A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.
A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.
Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification or release of tension at the time of committing the act.
A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
A PROTEIN O-METHYLTRANSFERASE that recognizes and catalyzes the methyl esterification of ISOASPARTIC ACID and D-ASPARTIC ACID residues in peptides and proteins. It initiates the repair of proteins damaged by the spontaneous decomposition of normal L-aspartic acid and L-asparagine residues.
Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.
'Nerve tissue proteins' are specialized proteins found within the nervous system's biological tissue, including neurofilaments, neuronal cytoskeletal proteins, and neural cell adhesion molecules, which facilitate structural support, intracellular communication, and synaptic connectivity essential for proper neurological function.
A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.
Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.
An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.
An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.
An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.
This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.
Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.
A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.
A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.

Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro. (1/1546)

alpha-Synuclein is a soluble presynaptic protein which is pathologically redistributed within intracellular lesions characteristic of several neurodegenerative diseases. Here we demonstrate that wild type and two mutant forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --> Pro and Ala53 --> Thr) self-aggregate and assemble into 10-19-nm-wide filaments with distinct morphologies under defined in vitro conditions. Immunogold labeling demonstrates that the central region of all these filaments are more robustly labeled than the N-terminal or C-terminal regions, suggesting that the latter regions are buried within the filaments. Since in vitro generated alpha-synuclein filaments resemble the major ultrastructural elements of authentic Lewy bodies that are hallmark lesions of Parkinson's disease, we propose that self-aggregating alpha-synuclein is the major subunit protein of these filamentous lesions.  (+info)

Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation. (2/1546)

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD, but their pathogenic mechanism is not understood. Here we show that both wild type and mutant alpha-synuclein form insoluble fibrillar aggregates with antiparallel beta-sheet structure upon incubation at physiological temperature in vitro. Importantly, aggregate formation is accelerated by both PD-linked mutations. Under the experimental conditions, the lag time for the formation of precipitable aggregates is about 280 h for the wild type protein, 180 h for the A30P mutant, and only 100 h for the A53T mutant protein. These data suggest that the formation of alpha-synuclein aggregates could be a critical step in PD pathogenesis, which is accelerated by the PD-linked mutations.  (+info)

Copper(II)-induced self-oligomerization of alpha-synuclein. (3/1546)

alpha-Synuclein is a component of the abnormal protein depositions in senile plaques and Lewy bodies of Alzheimer's disease (AD) and Parkinson's disease respectively. The protein was suggested to provide a possible nucleation centre for plaque formation in AD via selective interaction with amyloid beta/A4 protein (Abeta). We have shown previously that alpha-synuclein has experienced self-oligomerization when Abeta25-35 was present in an orientation-specific manner in the sequence. Here we examine this biochemically specific self-oligomerization with the use of various metals. Strikingly, copper(II) was the most effective metal ion affecting alpha-synuclein to form self-oligomers in the presence of coupling reagents such as dicyclohexylcarbodi-imide or N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. The size distribution of the oligomers indicated that monomeric alpha-synuclein was oligomerized sequentially. The copper-induced oligomerization was shown to be suppressed as the acidic C-terminus of alpha-synuclein was truncated by treatment with endoproteinase Asp-N. In contrast, the Abeta25-35-induced oligomerizations of the intact and truncated forms of alpha-synuclein were not affected. This clearly indicated that the copper-induced oligomerization was dependent on the acidic C-terminal region and that its underlying biochemical mechanism was distinct from that of the Abeta25-35-induced oligomerization. Although the physiological or pathological relevance of the oligomerization remains currently elusive, the common outcome of alpha-synuclein on treatment with copper or Abeta25-35 might be useful in understanding neurodegenerative disorders in molecular terms. In addition, abnormal copper homoeostasis could be considered as one of the risk factors for the development of disorders such as AD or Parkinson's disease.  (+info)

alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease. (4/1546)

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major components of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD. alpha-Synuclein fibrils similar to the Lewy body filaments can be formed in vitro, and we have shown recently that both PD-linked mutations accelerate their formation. This study addresses the mechanism of alpha-synuclein aggregation: we show that (i) it is a nucleation-dependent process that can be seeded by aggregated alpha-synuclein functioning as nuclei, (ii) this fibril growth follows first-order kinetics with respect to alpha-synuclein concentration, and (iii) mutant alpha-synuclein can seed the aggregation of wild type alpha-synuclein, which leads us to predict that the Lewy bodies of familial PD patients with alpha-synuclein mutations will contain both, the mutant and the wild type protein. Finally (iv), we show that wild type and mutant forms of alpha-synuclein do not differ in their critical concentrations. These results suggest that differences in aggregation kinetics of alpha-synucleins cannot be explained by differences in solubility but are due to different nucleation rates. Consequently, alpha-synuclein nucleation may be the rate-limiting step for the formation of Lewy body alpha-synuclein fibrils in Parkinson's disease.  (+info)

alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. (5/1546)

alpha-Synuclein has been implicated in the pathophysiology of many neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. Mutations in alpha-synuclein cause some cases of familial PD (Polymeropoulos et al., 1997; Kruger et al., 1998). In addition, many neurodegenerative diseases show accumulation of alpha-synuclein in dystrophic neurites and in Lewy bodies (Spillantini et al., 1998). Here, we show that alpha-synuclein shares physical and functional homology with 14-3-3 proteins, which are a family of ubiquitous cytoplasmic chaperones. Regions of alpha-synuclein and 14-3-3 proteins share over 40% homology. In addition, alpha-synuclein binds to 14-3-3 proteins, as well as some proteins known to associate with 14-3-3, including protein kinase C, BAD, and extracellular regulated kinase, but not Raf-1. We also show that overexpression of alpha-synuclein inhibits protein kinase C activity. The association of alpha-synuclein with BAD and inhibition of protein kinase C suggests that increased expression of alpha-synuclein could be harmful. Consistent with this hypothesis, we observed that overexpression of wild-type alpha-synuclein is toxic, and overexpression of alpha-synuclein containing the A53T or A30P mutations exhibits even greater toxicity. The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases.  (+info)

Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies. (6/1546)

Alzheimer's disease and Parkinson's disease are the most common neurodegenerative diseases. They are characterized by the degeneration of selected populations of nerve cells that develop filamentous inclusions before degeneration. The neuronal inclusions of Alzheimer's disease are made of the microtubule-associated protein tau, in a hyperphosphorylated state. Recent work has shown that the filamentous inclusions of Parkinson's disease are made of the protein alpha-synuclein and that rare, familial forms of Parkinson's disease are caused by missense mutations in the alpha-synuclein gene. Besides Parkinson's disease, the filamentous inclusions of two additional neurodegenerative diseases, namely dementia with Lewy bodies and multiple system atrophy, have also been found to be made of alpha-synuclein. Abundant filamentous tau inclusions are not limited to Alzheimer's disease. They are the defining neuropathological characteristic of frontotemporal dementias such as Pick's disease, and of progressive supranuclear palsy and corticobasal degeneration. The recent discovery of mutations in the tau gene in familial forms of frontotemporal dementia has provided a direct link between tau dysfunction and dementing disease. The new work has established that tauopathies and alpha-synucleinopathies account for most late-onset neurodegenerative diseases in man. The formation of intracellular filamentous inclusions might be the gain of toxic function that leads to the demise of affected brain cells.  (+info)

alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356. (7/1546)

alpha-Synuclein has been implicated in the pathogenesis of several neurodegenerative disorders based on the direct linking of missense mutations in alpha-synuclein to autosomal dominant Parkinson's disease and its presence in Lewy-like lesions. To gain insight into alpha-synuclein functions, we have investigated whether it binds neuronal proteins and modulates their functional state. The microtubule-associated protein tau was identified as a ligand by alpha-synuclein affinity chromatography of human brain cytosol. Direct binding assays using (125)I-labeled human tau40 demonstrated a reversible binding with a IC(50) about 50 pM. The interacting domains were localized to the C terminus of alpha-synuclein and the microtubule binding region of tau as determined by protein fragmentation and the use of recombinant peptides. High concentrations of tubulin inhibited the binding between tau and alpha-synuclein. Functionally, alpha-synuclein stimulated the protein kinase A-catalyzed phosphorylation of tau serine residues 262 and 356 as determined using a phospho-epitope-specific antibody. We propose that alpha-synuclein modulates the phosphorylation of soluble axonal tau and thereby indirectly affects the stability of axonal microtubules.  (+info)

The genetics of disorders with synuclein pathology and parkinsonism. (8/1546)

Despite being considered the archetypal non-genetic neurological disorder, genetic analysis of Parkinson's disease has shown that there are at least three genetic loci. Furthermore, these analyses have suggested that the phenotype of the pathogenic loci is wider than simple Parkinson's disease and may include Lewy body dementia and some forms of essential tremor. Identification of alpha-synuclein as the first of the loci involved in Parkinson's disease and the identification of this protein in pathological deposits in other disorders has led to the suggestion that it may share pathogenic mechanisms with multiple system atrophy, Alzheimer's disease and prion disease and that these mechanisms are related to a synuclein pathway to cell death. Finally, genetic analysis of the synuclein diseases and the tau diseases may indicate that this synuclein pathway is an alternative to the tau pathway to cell death.  (+info)

Alpha-synuclein is a protein that is primarily found in neurons (nerve cells) in the brain. It is encoded by the SNCA gene and is abundantly expressed in presynaptic terminals, where it is believed to play a role in the regulation of neurotransmitter release.

In certain neurological disorders, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, alpha-synuclein can form aggregates known as Lewy bodies and Lewy neurites. These aggregates are a pathological hallmark of these diseases and are believed to contribute to the death of nerve cells, leading to the symptoms associated with these disorders.

The precise function of alpha-synuclein is not fully understood, but it is thought to be involved in various cellular processes such as maintaining the structure of the presynaptic terminal, regulating synaptic vesicle trafficking and neurotransmitter release, and protecting neurons from stress.

Synucleins are a family of small, heat-stable, water-soluble proteins that are primarily expressed in neurons. They are involved in various cellular processes such as modulating synaptic plasticity, vesicle trafficking, and neurotransmitter release. The most well-known members of this family are alpha-synuclein, beta-synuclein, and gamma-synuclein.

Abnormal accumulation and aggregation of alpha-synuclein into insoluble fibrils called Lewy bodies and Lewy neurites are hallmark features of several neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. These conditions are collectively referred to as synucleinopathies. The dysfunction and aggregation of alpha-synuclein are thought to contribute to the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, a region of the brain involved in motor control, leading to the characteristic symptoms observed in these disorders.

Gamma-synuclein is a protein that belongs to the synuclein family, which also includes alpha-synuclein and beta-synuclein. These proteins are abundantly expressed in the brain and are involved in various cellular processes such as vesicle trafficking, neurotransmitter release, and maintaining the structure of neurons.

Gamma-synuclein is primarily found in the central nervous system and is expressed at lower levels compared to alpha-synuclein. It has been identified as a component of Lewy bodies, which are intracellular inclusions found in the brains of patients with Parkinson's disease and other synucleinopathies. However, its precise role in these diseases remains unclear.

Like other synucleins, gamma-synuclein can form aggregates under certain conditions, and this property has been suggested to contribute to its pathological role in neurodegenerative disorders. Additionally, gamma-synuclein has been implicated in cancer, where it promotes tumor growth and metastasis.

Overall, further research is needed to fully understand the physiological and pathological functions of gamma-synuclein.

Impulse Control Disorders (ICDs) are a group of psychiatric conditions characterized by the failure to resist an impulse, drive, or temptation to perform an act that is harmful to oneself or others. This leads to negative consequences such as distress, anxiety, or disruption in social, occupational, or other important areas of functioning.

The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) recognizes several specific ICDs, including:

1. Kleptomania - the recurrent failure to resist impulses to steal items, even though they are not needed for personal use or financial gain.
2. Pyromania - the deliberate and purposeful fire-setting on more than one occasion.
3. Intermittent Explosive Disorder - recurrent behavioral outbursts representing a failure to control aggressive impulses, resulting in serious assaultive acts or destruction of property.
4. Pathological Gambling - persistent and recurrent maladaptive gambling behavior that disrupts personal, family, or vocational pursuits.
5. Internet Gaming Disorder - the excessive and prolonged use of the internet for gaming, which leads to clinically significant impairment or distress.

These disorders are typically associated with a range of emotional, cognitive, and behavioral symptoms that can vary depending on the specific disorder and individual presentation. Treatment often involves a combination of psychotherapy, medication, and self-help strategies to manage symptoms and improve overall functioning.

Beta-synuclein is a protein that is encoded by the SNCB gene in humans. It is a member of the synuclein family, which also includes alpha-synuclein and gamma-synuclein. Beta-synuclein is primarily found in the brain and is expressed at high levels in neurons.

Like alpha-synuclein, beta-synuclein has been shown to interact with lipids and play a role in the maintenance of synaptic function. However, unlike alpha-synuclein, which can form aggregates that are associated with neurodegenerative diseases such as Parkinson's disease and dementia with Lewy bodies, beta-synuclein does not appear to form aggregates under normal physiological conditions.

Some studies have suggested that beta-synuclein may play a protective role in the brain by inhibiting the aggregation of alpha-synuclein. However, other studies have suggested that beta-synuclein may contribute to neurodegeneration in certain contexts, such as in the presence of mutations or under conditions of cellular stress.

Overall, while the exact functions and regulatory mechanisms of beta-synuclein are still being elucidated, it is clear that this protein plays important roles in neuronal function and may have implications for neurodegenerative diseases.

Parkinson's disease is a progressive neurodegenerative disorder that affects movement. It is characterized by the death of dopamine-producing cells in the brain, specifically in an area called the substantia nigra. The loss of these cells leads to a decrease in dopamine levels, which results in the motor symptoms associated with Parkinson's disease. These symptoms can include tremors at rest, stiffness or rigidity of the limbs and trunk, bradykinesia (slowness of movement), and postural instability (impaired balance and coordination). In addition to these motor symptoms, non-motor symptoms such as cognitive impairment, depression, anxiety, and sleep disturbances are also common in people with Parkinson's disease. The exact cause of Parkinson's disease is unknown, but it is thought to be a combination of genetic and environmental factors. There is currently no cure for Parkinson's disease, but medications and therapies can help manage the symptoms and improve quality of life.

Dopamine is a type of neurotransmitter, which is a chemical messenger that transmits signals in the brain and nervous system. It plays several important roles in the body, including:

* Regulation of movement and coordination
* Modulation of mood and motivation
* Control of the reward and pleasure centers of the brain
* Regulation of muscle tone
* Involvement in memory and attention

Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area. It is released by neurons (nerve cells) and binds to specific receptors on other neurons, where it can either excite or inhibit their activity.

Abnormalities in dopamine signaling have been implicated in several neurological and psychiatric conditions, including Parkinson's disease, schizophrenia, and addiction.

Protein D-aspartate-L-isoaspartate methyltransferase (PCMT or PRMT5) is an enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to the side chain nitrogen atom of a specific aspartate or glutamate residue on protein substrates. This enzyme plays a crucial role in the maintenance of protein structure and function by correcting the spontaneous deamidation of asparagine and isomerization of aspartate to isoaspartate residues, which can lead to protein aggregation and loss of function. PCMT also regulates various cellular processes, including transcription, RNA processing, DNA damage repair, and signal transduction, by modifying the activity or localization of its target proteins.

Lewy bodies are abnormal aggregates of alpha-synuclein protein that develop in nerve cells (neurons) in the brain. They are named after Frederick Lewy, a German-American neurologist who discovered them while working with Dr. Alois Alzheimer. The presence of Lewy bodies is a hallmark feature of Lewy body dementia, which includes both Parkinson's disease dementia and dementia with Lewy bodies.

Lewy bodies can lead to the dysfunction and death of neurons in areas of the brain that control movement, cognition, and behavior. This can result in a range of symptoms, including motor impairments, cognitive decline, visual hallucinations, and mood changes. The exact role of Lewy bodies in the development and progression of these disorders is not fully understood, but they are believed to contribute to the neurodegenerative process that underlies these conditions.

Nerve tissue proteins are specialized proteins found in the nervous system that provide structural and functional support to nerve cells, also known as neurons. These proteins include:

1. Neurofilaments: These are type IV intermediate filaments that provide structural support to neurons and help maintain their shape and size. They are composed of three subunits - NFL (light), NFM (medium), and NFH (heavy).

2. Neuronal Cytoskeletal Proteins: These include tubulins, actins, and spectrins that provide structural support to the neuronal cytoskeleton and help maintain its integrity.

3. Neurotransmitter Receptors: These are specialized proteins located on the postsynaptic membrane of neurons that bind neurotransmitters released by presynaptic neurons, triggering a response in the target cell.

4. Ion Channels: These are transmembrane proteins that regulate the flow of ions across the neuronal membrane and play a crucial role in generating and transmitting electrical signals in neurons.

5. Signaling Proteins: These include enzymes, receptors, and adaptor proteins that mediate intracellular signaling pathways involved in neuronal development, differentiation, survival, and death.

6. Adhesion Proteins: These are cell surface proteins that mediate cell-cell and cell-matrix interactions, playing a crucial role in the formation and maintenance of neural circuits.

7. Extracellular Matrix Proteins: These include proteoglycans, laminins, and collagens that provide structural support to nerve tissue and regulate neuronal migration, differentiation, and survival.

Parkinsonian disorders are a group of neurological conditions characterized by motor symptoms such as bradykinesia (slowness of movement), rigidity, resting tremor, and postural instability. These symptoms are caused by the degeneration of dopamine-producing neurons in the brain, particularly in the substantia nigra pars compacta.

The most common Parkinsonian disorder is Parkinson's disease (PD), which is a progressive neurodegenerative disorder. However, there are also several other secondary Parkinsonian disorders, including:

1. Drug-induced parkinsonism: This is caused by the use of certain medications, such as antipsychotics and metoclopramide.
2. Vascular parkinsonism: This is caused by small vessel disease in the brain, which can lead to similar symptoms as PD.
3. Dementia with Lewy bodies (DLB): This is a type of dementia that shares some features with PD, such as the presence of alpha-synuclein protein clumps called Lewy bodies.
4. Progressive supranuclear palsy (PSP): This is a rare brain disorder that affects movement, gait, and eye movements.
5. Multiple system atrophy (MSA): This is a progressive neurodegenerative disorder that affects multiple systems in the body, including the autonomic nervous system, motor system, and cerebellum.
6. Corticobasal degeneration (CBD): This is a rare neurological disorder that affects both movement and cognition.

It's important to note that while these disorders share some symptoms with PD, they have different underlying causes and may require different treatments.

Neurodegenerative diseases are a group of disorders characterized by progressive and persistent loss of neuronal structure and function, often leading to cognitive decline, functional impairment, and ultimately death. These conditions are associated with the accumulation of abnormal protein aggregates, mitochondrial dysfunction, oxidative stress, chronic inflammation, and genetic mutations in the brain. Examples of neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), and Spinal Muscular Atrophy (SMA). The underlying causes and mechanisms of these diseases are not fully understood, and there is currently no cure for most neurodegenerative disorders. Treatment typically focuses on managing symptoms and slowing disease progression.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Alpha 1-antitrypsin (AAT, or α1-antiproteinase, A1AP) is a protein that is primarily produced by the liver and released into the bloodstream. It belongs to a group of proteins called serine protease inhibitors, which help regulate inflammation and protect tissues from damage caused by enzymes involved in the immune response.

Alpha 1-antitrypsin is particularly important for protecting the lungs from damage caused by neutrophil elastase, an enzyme released by white blood cells called neutrophils during inflammation. In the lungs, AAT binds to and inhibits neutrophil elastase, preventing it from degrading the extracellular matrix and damaging lung tissue.

Deficiency in alpha 1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD) and liver disease. The most common cause of AAT deficiency is a genetic mutation that results in abnormal folding and accumulation of the protein within liver cells, leading to reduced levels of functional AAT in the bloodstream. This condition is called alpha 1-antitrypsin deficiency (AATD) and can be inherited in an autosomal codominant manner. Individuals with severe AATD may require augmentation therapy with intravenous infusions of purified human AAT to help prevent lung damage.

The brain is the central organ of the nervous system, responsible for receiving and processing sensory information, regulating vital functions, and controlling behavior, movement, and cognition. It is divided into several distinct regions, each with specific functions:

1. Cerebrum: The largest part of the brain, responsible for higher cognitive functions such as thinking, learning, memory, language, and perception. It is divided into two hemispheres, each controlling the opposite side of the body.
2. Cerebellum: Located at the back of the brain, it is responsible for coordinating muscle movements, maintaining balance, and fine-tuning motor skills.
3. Brainstem: Connects the cerebrum and cerebellum to the spinal cord, controlling vital functions such as breathing, heart rate, and blood pressure. It also serves as a relay center for sensory information and motor commands between the brain and the rest of the body.
4. Diencephalon: A region that includes the thalamus (a major sensory relay station) and hypothalamus (regulates hormones, temperature, hunger, thirst, and sleep).
5. Limbic system: A group of structures involved in emotional processing, memory formation, and motivation, including the hippocampus, amygdala, and cingulate gyrus.

The brain is composed of billions of interconnected neurons that communicate through electrical and chemical signals. It is protected by the skull and surrounded by three layers of membranes called meninges, as well as cerebrospinal fluid that provides cushioning and nutrients.

Adrenergic receptors are a type of G protein-coupled receptor that bind and respond to catecholamines, such as epinephrine (adrenaline) and norepinephrine (noradrenaline). Alpha adrenergic receptors (α-ARs) are a subtype of adrenergic receptors that are classified into two main categories: α1-ARs and α2-ARs.

The activation of α1-ARs leads to the activation of phospholipase C, which results in an increase in intracellular calcium levels and the activation of various signaling pathways that mediate diverse physiological responses such as vasoconstriction, smooth muscle contraction, and cell proliferation.

On the other hand, α2-ARs are primarily located on presynaptic nerve terminals where they function to inhibit the release of neurotransmitters, including norepinephrine. The activation of α2-ARs also leads to the inhibition of adenylyl cyclase and a decrease in intracellular cAMP levels, which can mediate various physiological responses such as sedation, analgesia, and hypotension.

Overall, α-ARs play important roles in regulating various physiological functions, including cardiovascular function, mood, and cognition, and are also involved in the pathophysiology of several diseases, such as hypertension, heart failure, and neurodegenerative disorders.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the body's response to low oxygen levels, also known as hypoxia. HIF-1 is a heterodimeric protein composed of two subunits: an alpha subunit (HIF-1α) and a beta subunit (HIF-1β).

The alpha subunit, HIF-1α, is the regulatory subunit that is subject to oxygen-dependent degradation. Under normal oxygen conditions (normoxia), HIF-1α is constantly produced in the cell but is rapidly degraded by proteasomes due to hydroxylation of specific proline residues by prolyl hydroxylase domain-containing proteins (PHDs). This hydroxylation reaction requires oxygen as a substrate, and under hypoxic conditions, the activity of PHDs is inhibited, leading to the stabilization and accumulation of HIF-1α.

Once stabilized, HIF-1α translocates to the nucleus, where it heterodimerizes with HIF-1β and binds to hypoxia-responsive elements (HREs) in the promoter regions of target genes. This binding results in the activation of gene transcription programs that promote cellular adaptation to low oxygen levels. These adaptive responses include increased erythropoiesis, angiogenesis, glucose metabolism, and pH regulation, among others.

Therefore, HIF-1α is a critical regulator of the body's response to hypoxia, and its dysregulation has been implicated in various pathological conditions, including cancer, cardiovascular disease, and neurodegenerative disorders.

The alpha7 nicotinic acetylcholine receptor (α7nAChR) is a type of cholinergic receptor found in the nervous system that is activated by the neurotransmitter acetylcholine. It is a ligand-gated ion channel that is widely distributed throughout the central and peripheral nervous systems, including in the hippocampus, cortex, thalamus, and autonomic ganglia.

The α7nAChR is composed of five subunits arranged around a central pore, and it has a high permeability to calcium ions (Ca2+). When acetylcholine binds to the receptor, it triggers a conformational change that opens the ion channel, allowing Ca2+ to flow into the cell. This influx of Ca2+ can activate various intracellular signaling pathways and have excitatory or inhibitory effects on neuronal activity, depending on the location and function of the receptor.

The α7nAChR has been implicated in a variety of physiological processes, including learning and memory, attention, sensory perception, and motor control. It has also been studied as a potential therapeutic target for various neurological and psychiatric disorders, such as Alzheimer's disease, schizophrenia, and pain.

Integrin α3β1 is a type of cell surface receptor that is widely expressed in various tissues, including epithelial and endothelial cells. It is composed of two subunits, α3 and β1, which form a heterodimeric complex that plays a crucial role in cell-matrix adhesion and signaling.

Integrin α3β1 binds to several extracellular matrix proteins, such as laminin, fibronectin, and collagen IV, and mediates various cellular functions, including cell migration, proliferation, differentiation, and survival. It also participates in intracellular signaling pathways that regulate cell behavior and tissue homeostasis.

Mutations in the genes encoding integrin α3β1 have been associated with several human diseases, including blistering skin disorders, kidney disease, and cancer. Therefore, understanding the structure, function, and regulation of integrin α3β1 is essential for developing new therapeutic strategies to treat these conditions.

Integrin α4 (also known as CD49d or ITGA4) is a subunit of integrin proteins, which are heterodimeric transmembrane receptors that mediate cell-cell and cell-extracellular matrix interactions. Integrin α4 typically pairs with β1 (CD29 or ITGB1) or β7 (ITGB7) subunits to form integrins α4β1 and α4β7, respectively.

Integrin α4β1, also known as very late antigen-4 (VLA-4), is widely expressed on various hematopoietic cells, including lymphocytes, monocytes, eosinophils, and basophils. It plays crucial roles in the adhesion, migration, and homing of these cells to secondary lymphoid organs, as well as in the recruitment of immune cells to inflammatory sites. Integrin α4β1 binds to its ligands, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin, via the arginine-glycine-aspartic acid (RGD) motif.

Integrin α4β7, on the other hand, is primarily expressed on gut-homing lymphocytes and interacts with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), a protein mainly found in the high endothelial venules of intestinal Peyer's patches and mesenteric lymph nodes. This interaction facilitates the trafficking of immune cells to the gastrointestinal tract, where they participate in immune responses against pathogens and maintain gut homeostasis.

In summary, Integrin α4 is a crucial subunit of integrins that mediates cell adhesion, migration, and homing to specific tissues through its interactions with various ligands. Dysregulation of integrin α4 has been implicated in several pathological conditions, including inflammatory diseases, autoimmune disorders, and cancer metastasis.

Integrin α6 (also known as CD49f) is a type of integrin, which is a heterodimeric transmembrane receptor that mediates cell-cell and cell-extracellular matrix (ECM) interactions. Integrins play crucial roles in various biological processes such as cell adhesion, migration, proliferation, differentiation, and survival.

Integrin α6 is a 130 kDa glycoprotein that pairs with integrin β1, β4 or β5 to form three distinct heterodimeric complexes: α6β1, α6β4, and α6β5. Among these, the α6β4 integrin is the most extensively studied. It specifically binds to laminins in the basement membrane and plays essential roles in maintaining epithelial tissue architecture and function.

The α6β4 integrin has a unique structure with an extended cytoplasmic domain of β4 that can interact with intracellular signaling molecules, cytoskeletal proteins, and other adhesion receptors. This interaction allows the formation of stable adhesion complexes called hemidesmosomes, which anchor epithelial cells to the basement membrane and provide mechanical stability to tissues.

Mutations in integrin α6 or its partners can lead to various human diseases, including epidermolysis bullosa, a group of inherited skin disorders characterized by fragile skin and mucous membranes that blister and tear easily.

Integrin α5β1, also known as very late antigen-5 (VLA-5) or fibronectin receptor, is a heterodimeric transmembrane receptor protein composed of two subunits: α5 and β1. This integrin is widely expressed in various cell types, including endothelial cells, smooth muscle cells, and fibroblasts.

Integrin α5β1 plays a crucial role in mediating cell-matrix adhesion by binding to the arginine-glycine-aspartic acid (RGD) sequence present in the extracellular matrix protein fibronectin. The interaction between integrin α5β1 and fibronectin is essential for various biological processes, such as cell migration, proliferation, differentiation, and survival. Additionally, this integrin has been implicated in several pathological conditions, including tumor progression, angiogenesis, and fibrosis.

Integrin α4β1, also known as Very Late Antigen-4 (VLA-4), is a heterodimeric transmembrane receptor protein composed of two subunits, α4 and β1. It is involved in various cellular activities such as adhesion, migration, and signaling. This integrin plays a crucial role in the immune system by mediating the interaction between leukocytes (white blood cells) and the endothelial cells that line blood vessels. The activation of Integrin α4β1 allows leukocytes to roll along and then firmly adhere to the endothelium, followed by their migration into surrounding tissues, particularly during inflammation and immune responses. Additionally, Integrin α4β1 also interacts with extracellular matrix proteins such as fibronectin and helps regulate cell survival, proliferation, and differentiation in various cell types.

Interleukin-1 alpha (IL-1α) is a member of the interleukin-1 cytokine family, which plays a crucial role in the regulation of inflamation and immune responses. IL-1α is primarily produced by activated macrophages, epithelial cells, and fibroblasts. It is a potent proinflammatory cytokine that binds to the interleukin-1 receptor (IL-1R) and activates signaling pathways leading to the expression of genes involved in inflammation, fever, and cellular activation. IL-1α is involved in various physiological processes such as hematopoiesis, bone remodeling, and response to infection or injury. Dysregulation of IL-1α has been implicated in several pathological conditions including autoimmune diseases, atherosclerosis, and cancer.

Integrin α2β1, also known as very late antigen-2 (VLA-2) or laminin receptor, is a heterodimeric transmembrane receptor protein composed of α2 and β1 subunits. It belongs to the integrin family of adhesion molecules that play crucial roles in cell-cell and cell-extracellular matrix (ECM) interactions.

Integrin α2β1 is widely expressed on various cell types, including fibroblasts, endothelial cells, smooth muscle cells, and some hematopoietic cells. It functions as a receptor for several ECM proteins, such as collagens (type I, II, III, and V), laminin, and fibronectin. The binding of integrin α2β1 to these ECM components mediates cell adhesion, migration, proliferation, differentiation, and survival, thereby regulating various physiological and pathological processes, such as tissue repair, angiogenesis, inflammation, and tumor progression.

In addition, integrin α2β1 has been implicated in several diseases, including fibrosis, atherosclerosis, and cancer. Therefore, targeting this integrin with therapeutic strategies may provide potential benefits for treating these conditions.

Alpha-1 adrenergic receptors (also known as α1-adrenoreceptors) are a type of G protein-coupled receptor that binds catecholamines, such as norepinephrine and epinephrine. These receptors are primarily found in the smooth muscle of various organs, including the vasculature, heart, liver, kidneys, gastrointestinal tract, and genitourinary system.

When an alpha-1 adrenergic receptor is activated by a catecholamine, it triggers a signaling cascade that leads to the activation of phospholipase C, which in turn activates protein kinase C and increases intracellular calcium levels. This ultimately results in smooth muscle contraction, increased heart rate and force of contraction, and vasoconstriction.

Alpha-1 adrenergic receptors are also found in the central nervous system, where they play a role in regulating wakefulness, attention, and anxiety. There are three subtypes of alpha-1 adrenergic receptors (α1A, α1B, and α1D), each with distinct physiological roles and pharmacological properties.

In summary, alpha-1 adrenergic receptors are a type of G protein-coupled receptor that binds catecholamines and mediates various physiological responses, including smooth muscle contraction, increased heart rate and force of contraction, vasoconstriction, and regulation of wakefulness and anxiety.

Integrin α5 (also known as CD49e) is a subunit of the heterodimeric integrin receptor called very late antigen-5 (VLA-5). Integrins are transmembrane adhesion receptors that play crucial roles in cell-cell and cell-extracellular matrix interactions. The α5β1 integrin, formed by the association of α5 and β1 subunits, specifically recognizes and binds to fibronectin, a major extracellular matrix protein. This binding event is essential for various biological processes such as cell migration, proliferation, differentiation, and survival.

In summary, Integrin alpha5 (α5) is an essential subunit of the α5β1 integrin receptor that mediates cell-fibronectin interactions and contributes to several vital cellular functions.

Integrin α1β1, also known as Very Late Antigen-1 (VLA-1) or CD49a/CD29, is a heterodimeric transmembrane receptor protein composed of α1 and β1 subunits. It belongs to the integrin family of adhesion molecules that play crucial roles in cell-cell and cell-extracellular matrix (ECM) interactions.

Integrin α1β1 is primarily expressed on various cell types, including fibroblasts, endothelial cells, smooth muscle cells, and some immune cells. This integrin binds to several ECM proteins, such as collagens (type I, II, III, IV), laminin, and fibronectin, mediating cell adhesion, migration, proliferation, differentiation, and survival. Additionally, α1β1 integrin has been implicated in various physiological and pathological processes, such as tissue repair, fibrosis, and tumor progression.

Alpha-2 adrenergic receptors are a type of G protein-coupled receptor that binds catecholamines, such as norepinephrine and epinephrine. These receptors are widely distributed in the central and peripheral nervous system, as well as in various organs and tissues throughout the body.

Activation of alpha-2 adrenergic receptors leads to a variety of physiological responses, including inhibition of neurotransmitter release, vasoconstriction, and reduced heart rate. These receptors play important roles in regulating blood pressure, pain perception, and various cognitive and emotional processes.

There are several subtypes of alpha-2 adrenergic receptors, including alpha-2A, alpha-2B, and alpha-2C, which may have distinct physiological functions and be targeted by different drugs. For example, certain medications used to treat hypertension or opioid withdrawal target alpha-2 adrenergic receptors to produce their therapeutic effects.

Integrin α6β1, also known as CD49f/CD29, is a heterodimeric transmembrane receptor protein composed of α6 and β1 subunits. It is widely expressed in various tissues, including epithelial cells, endothelial cells, fibroblasts, and hematopoietic cells. Integrin α6β1 plays a crucial role in cell-matrix adhesion, particularly to the laminin component of the extracellular matrix (ECM). This receptor is involved in various biological processes such as cell migration, proliferation, differentiation, and survival. Additionally, integrin α6β1 has been implicated in tumor progression, metastasis, and drug resistance in certain cancers.

Therefore, NACP is now referred to as human alpha-synuclein. Alpha-synuclein is a synuclein protein of unknown function ... which contain rich cytosolic alpha-synuclein but very low levels of mitochondrial alpha-synuclein. It has been shown that alpha ... Alpha-synuclein (aSyn) is a protein that, in humans, is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that ... The human alpha-synuclein protein is made of 140 amino acids. An alpha-synuclein fragment, known as the non-amyloid beta (non- ...
... alpha-synuclein, beta-synuclein, and gamma-synuclein. Interest in the synuclein family began when alpha-synuclein was found to ... Alpha-synuclein InterPro: IPR002460 Beta-synuclein InterPro: IPR002461 Gamma-synuclein InterPro: IPR002462 Normal cellular ... All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid- ... Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally ...
2006). "Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression". Hum. Mol. Genet ... 2005). "beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein". J. Biol. Chem. 280 (9): 7562 ... 1997). "Binding of Abeta to alpha- and beta-synucleins: identification of segments in alpha-synuclein/NAC precursor that bind ... Thus, beta-synuclein may protect the central nervous system from the neurotoxic effects of alpha-synuclein and provide a novel ...
2002). "Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly ... Gamma-synuclein is a protein that in humans is encoded by the SNCG gene. Synuclein-gamma is a member of the synuclein family of ... Gamma-synuclein is the least conserved of the synuclein proteins. Gamma-Synucleins expression in breast tumors is a marker for ... 2003). "Platelet alpha- and gamma-synucleins in Parkinson's disease and normal control subjects". J. Alzheimer's Dis. 4 (4): ...
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature ... alpha-synuclein was discovered to be the major component of Lewy bodies within brain cells of PD patients; according to the ... alpha-synuclein. Lazzarini worked with the Italian Instituto de Scienze Neurologiche to get blood samples from the family ... that fragments of alpha-synuclein bind to other proteins to form the Lewy body, an insoluble proteinaceous material ...
The NIH team and a team led by Maria Grazia Spillantini reported on alpha-synuclein deposits in Lewy bodies as well as alpha- ... Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997). "Alpha-synuclein in Lewy bodies". Nature. 388 ( ... Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998). "Alpha synuclein in neurodegenerative disorders ... 1997). "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease". Science. 276 (5321): 2045-7. doi ...
Alpha-synuclein modulates DNA repair processes, including repair of DNA double-strand breaks (DSBs) by the process of non- ... July 2019). "Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders". ... Cortical Lewy bodies are also composed of alpha-synuclein fibrils, but are less defined and lack halos. This kind of Lewy body ... Ishizawa T, Mattila P, Davies P, Wang D, Dickson DW (April 2003). "Colocalization of tau and alpha-synuclein epitopes in Lewy ...
... alpha-synuclein. Within days of the publication of the PARK1 findings, alpha-synuclein was discovered to be the major component ... Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature ... Schulz-Schaeffer WJ (August 2010). "The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, ... "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease". Science. 276 (5321): 2045-7. doi:10.1126 ...
She is most noted for identifying the protein alpha-synuclein as the major component of Lewy bodies, the characteristic protein ... In particular her work studies the role of microtubule-associated protein tau and alpha-synuclein aggregation in the ... "Alpha-synuclein in Lewy bodies". Nature. 388 (6645): 839-40. Bibcode:1997Natur.388..839G. doi:10.1038/42166. PMID 9278044. ...
The conformation of the alpha-synuclein is different from that of alpha-synuclein in Lewy bodies. The disease probably starts ... A modified form of the alpha-synuclein protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with ... November 1998). "NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic ... September 2009). "Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy". PLOS ONE. 4 ( ...
Preclinical research also targets alpha-synuclein. Selegiline is in a group of medications called monoamine oxidase type B (MAO ...
It shows a 60-times magnification of the alpha synuclein intraneuronal inclusions aggregated to form Lewy bodies. Stains used: ... mouse monoclonal alpha-synuclein antibody; counterstained with Mayer's haematoxylin., retrieved 2021-12-10 v t e (Cell biology ...
Moussaud S, Jones DR, Moussaud-Lamodière EL, Delenclos M, Ross OA, McLean PJ (October 2014). "Alpha-synuclein and tau: ... Tauopathies are often overlapped with synucleinopathies, possibly due to interaction between the synuclein and tau proteins. ...
Alpha-synuclein modulates DNA repair processes, including the repair of DNA double-strand breaks by the non-homologous end ... Alpha-synuclein deposits can affect the cardiac muscle and blood vessels. Almost all people with synucleinopathies have ... The DNA repair function of alpha-synuclein appears to be compromised in Lewy body inclusion bearing neurons, and this may ... October 2014). "Alpha-synuclein and tau: teammates in neurodegeneration?". Mol Neurodegener. 9: 43. doi:10.1186/1750-1326-9-43 ...
Kawahara K, Hashimoto M, Bar-On P, Ho GJ, Crews L, Mizuno H, Rockenstein E, Imam SZ, Masliah E (March 2008). "alpha-Synuclein ... Parkin might promote aggregation of alpha-synuclein and synphilin-1 into Lewy bodies, which are conjugated to Lys63-linked poly ... Another parkin substrate, synphilin-1 (encoded by SNCAIP), is an alpha-synuclein interacting protein that is enriched in the ... Parkin (ligase) has been shown to interact with: Alpha-synuclein, CASK, CUL1, FBXW7 and GPR37, HSPA1A, HSPA8, Multisynthetase ...
October 2003). "alpha-Synuclein locus triplication causes Parkinson's disease". Science. 302 (5646): 841. doi:10.1126/science. ... One example of a whole gene repeat is the alpha-amylase 1 gene (AMY1) that encodes alpha-amylase which has a significant copy ... The globin gene family is an elaborate network of genes consisting of alpha and beta globin genes including genes that are ... and one type of amylase is encoded by the alpha-amylase gene (AMY1). The AMY1 locus, as well as the amylase enzyme, is one of ...
Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ... it is alpha-synuclein. In Huntington's disease, it is huntingtin. Transglutaminase substrates: Amyloid-beta, tau, alpha- ... Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. The main known risk factor is age. Mutations ... Notably, alpha-synuclein-ubiquitin complexes and aggregates are observed to accumulate in Lewy bodies within affected neurons. ...
... stands for "synuclein, alpha interacting protein" and can be signified by SNCAP_HUMAN, synphilin 1, synuclein, alpha ... "Entrez Gene: SNCAIP synuclein, alpha interacting protein (synphilin)". Neystat M, Rzhetskaya M, Kholodilov N, Burke RE (June ... Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM (2004). "Aggresomes formed by alpha-synuclein and synphilin-1 are ... The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic ...
Lee FJ, Liu F, Pristupa ZB, Niznik HB (April 2001). "Direct binding and functional coupling of alpha-synuclein to the dopamine ... Dopamine transporter has been shown to interact with: Alpha-synuclein, PICK1, and TGFB1I1. Apart from these innate protein- ... Wersinger C, Sidhu A (April 2003). "Attenuation of dopamine transporter activity by alpha-synuclein". Neuroscience Letters. 340 ...
"Glycosylation as an Inhibitor of Alpha-synuclein Aggregation". The Michael J. Fox Foundation for Parkinson's Research , ... As O-GlcNAc modification of α-synuclein has been found to inhibit its aggregation, elevating α-synuclein O-GlcNAc is being ... Solid-phase peptide synthesis was used to prepare full-length α-synuclein with an O-GlcNAc modification at T72. Thioflavin T ... For example, a nanobody recognizing a C-terminal EPEA sequence can direct OGT enzymatic activity to α-synuclein. Apoptosis, a ...
Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC (November 2005). "Alpha-synuclein cooperates with CSPalpha in ... 2005). "Characterization of the G alpha(s) regulator cysteine string protein". J. Biol. Chem. 280 (34): 30236-41. doi:10.1074/ ... "The synaptic vesicle protein CSP alpha prevents presynaptic degeneration". Neuron. 42 (2): 237-51. doi:10.1016/S0896-6273(04) ... encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis". American Journal ...
"Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein". The Journal of Biological Chemistry. 275 ( ... Pronin AN, Morris AJ, Surguchov A, Benovic JL (Aug 2000). "Synucleins are a novel class of substrates for G protein-coupled ... Zhou H, Yan F, Tai HH (Sep 2001). "Phosphorylation and desensitization of the human thromboxane receptor-alpha by G protein- ...
December 2017). "Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes". The Journal of Neuroscience. 37 ... Also, FABP proteins have recently been shown to interact with a protein called synuclein to cause mitochondrial damage. ... Cheng, A (2021). "Impact of fatty acid-binding proteins in α-Synuclein-induced mitochondrial injury in synucleinopathy". ...
Alpha-synuclein from Multiple system atrophy and TMEM106B. Scheres has been a member of the Board of Reviewing Editors for ... "Structures of alpha-synuclein filaments from multiple system atrophy". Nature. 585 (7825): 464-469. Bibcode:2020Natur.585..464S ...
... and Lewy bodies and neurites were found to be immunoreactive for alpha-synuclein. Thus, alpha-synuclein aggregation was ... The role of alpha-synuclein deposits is unclear, because individuals with no signs of DLB have been found on autopsy to have ... Rarely, mutations in SNCA, the gene for alpha-synuclein, or LRRK2, a gene for a kinase enzyme, can cause any of DLB, ... DLB was thought to be rare until it became easier to diagnose in the 1980s after the discovery of alpha-synuclein ...
The Road to Alpha-Synuclein Oligomerization in PD". Parkinson's Disease. 2011: 693761. doi:10.4061/2011/693761. PMC 3026982. ... Mutations of synuclein alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... Parkinson's disease is characterized by inclusions of a protein called alpha-synuclien (Lewy bodies) in affected neurons that ...
... overexpression in human neuroglioma cells transfected with mutant alpha-synuclein led to 50% less oligomeric alpha- ... April 2008). "Formation of toxic oligomeric alpha-synuclein species in living cells". PLOS ONE. 3 (4): e1867. Bibcode:2008PLoSO ... In breast cancer cell line (MCF7) has been found that not only Hsp90 interacted with estrogen receptor alpha (ERα) but also ... C-terminal domain - rich in alpha helical structure acts as a 'lid' for the substrate binding domain. The helical subdomain ...
"Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications". Ann Neurol. 55 (2): 174-9. doi:10.1002/ ...
"Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy". Science. 305 (5688): 1292-5. Bibcode:2004Sci ...
It inhibits PTK2B/RAFTK activity and regulates alpha-synuclein phosphorylation. It interacts with Signal-regulatory protein ... and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein ... RA receptor alpha in acute promyelocytic leukemia cells". The Journal of Biological Chemistry. 276 (25): 22375-81. doi:10.1074/ ... alpha and directs integrin-activated cytoskeletal reorganization in macrophages. GRCh38: Ensembl release 89: ENSG00000005020 - ...
Therefore, NACP is now referred to as human alpha-synuclein. Alpha-synuclein is a synuclein protein of unknown function ... which contain rich cytosolic alpha-synuclein but very low levels of mitochondrial alpha-synuclein. It has been shown that alpha ... Alpha-synuclein (aSyn) is a protein that, in humans, is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that ... The human alpha-synuclein protein is made of 140 amino acids. An alpha-synuclein fragment, known as the non-amyloid beta (non- ...
Point mutations in the alpha-synuclein gene have been demonstrated in familial PD and alpha-synuclein is a major component of ... The presynaptic protein alpha-synuclein is considered to play an important role in the pathophysiology of Parkinsons disease ( ... Point mutations in the alpha-synuclein gene have been demonstrated in familial PD and alpha-synuclein is a major component of ... Alteration in alpha-synuclein mRNA expression in Parkinsons disease Mov Disord. 2004 Feb;19(2):162-70. doi: 10.1002/mds.10683 ...
New research has advanced our understanding of a protein called alpha-synuclein, which is believed to play a central role in ... But alpha-synuclein is also present in brain cells of people without Parkinsons. We dont really know what this protein does ... Whats alpha-synuclein?. Its not clear exactly what causes someone to develop Parkinsons. Researchers are constantly piecing ... Alpha-synuclein is a protein that sticks together forming clumps within the brain cells affected in the condition. ...
An ability to visualize and quantify alpha-synuclein and tau aggregates in the brain would be valuable for diagnosing PD and ... In this study, we will develop imaging agents that can be used to detect alpha-synuclein and tau. Hypothesis: Highly selective ... Impact on Diagnosis/Treatment of Parkinsons disease: Detection of alpha-synuclein and tau deposits in the brain of PD and FTD ... Study Design: Compounds that bind selectively to alpha-synuclein and tau deposits will be assessed using a variety of binding ...
Clearance and deposition of extracellular alpha-synuclein aggregates in microglia. Biochem Biophys Res Commun. 2008 Aug 1;372(3 ...
Alpha synuclein monomer, Alpha-synuclein monomer, Alpha synuclein protein monomer, Alpha synuclein monomer, Alpha-synuclein ... Alpha-Synuclein (SNCA) is expressed predominantly in the brain, where it is concentrated in presynaptic nerve terminals (1). ... Alpha-synuclein is highly expressed in the mitochondria of the olfactory bulb, hippocampus, striatum and thalamus (2). ... Alpha synuclein monomers, SYN protein, Parkinson disease familial 1 Protein. Application:. Cell-based/Functional Assay, SDS- ...
Aggregation in this model is induced by the intrastriatal injection of α-synuclein pre-formed fibrils and recapitulates several ... Additionally, the immunoproteasome degrades α-synuclein fibrils more efficiently than the constitutive proteasome. This is the ... was elevated in response to α-synuclein aggregation. Increased levels and activity of the immunoproteasome were found in human ... "α-Synuclein aggregation is implicated in several neurodegenerative diseases, including Parkinsons disease (PD) and dementia ...
... lowered DNA methylation of alpha-synuclein gene, resulted in alpha-synuclein protein deposition, and elevated the ratio of LC3- ... The mechanistic studies showed that chronic reserpine exposure caused hypomethylation of the alpha-synuclein gene and up- ... Chronic reserpine exposure epigenetically elevated the levels of alpha-synuclein expression possible by lowering the DNA ... Roles of epigenetic upregulation of alpha-synuclein and autophagy impairment. ...
alpha Synuclein is primarily located at presynaptic terminals and is found membrane bound in dopaminergic neurons. Useful for ... alpha Synuclein is a member of a family of small, highly conserved proteins, including synuclein-alpha, -beta, and -gamma, and ... Synuclein-alpha is normally a soluble protein. Abnormal synuclein-alpha forms filamentous inclusions (Lewy bodies and Lewy ... Mutations in the synuclein-alpha gene (A53T and A30P) have been reported in several families with autosomal dominant ...
Galectin-3 shapes toxic alpha-synuclein strains in Parkinsons disease. *Mark. García-Revilla, Juan LU ; Boza-Serrano, Antonio ... Galectin-3 (GAL3), Lewy body (LB), Parkinsons disease (PD), α-synuclein (αSYN). in Acta Neuropathologica. volume. 146. issue. ... Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several ... Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several ...
... α-synuclein (α-syn) aggregation can lead to degeneration of dopaminergic neurons in the substantia nigra pars compacta ( SNpc ... DNAJB6 Suppresses Alpha-synuclein Induced Pathology in an Animal Model of Parkinsons Disease ... Keywords: Protein homeostasis, Parkinson`s Disease, Alpha-synuclein, Adeno Associated Virus, DNAJB6, Heat Shock Protein 70 ... Background: α-synuclein (α-syn) aggregation can lead to degeneration of dopaminergic neurons in the substantia nigra pars ...
Alpha-synuclein (SNCA) gene has been implicated in the development of rare forms of familial Parkinson disease (PD). Recently, ... Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain.. ... "Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain." ... "Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain." ...
Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage ... 2017). Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage. ... Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage ...
23andMe offers DNA testing with the most comprehensive ancestry breakdown, personalized health insights and more.
Wildtype and A30P Mutant Alpha-Synuclein Form Different Fibril Structures. P L o S One. 2013;8(7):e67713. doi: 10.1371/journal. ... Wildtype and A30P Mutant Alpha-Synuclein Form Different Fibril Structures. I: P L o S One. 2013 ; Bind 8, Nr. 7. ... Wildtype and A30P Mutant Alpha-Synuclein Form Different Fibril Structures. Søren Bang Nielsen, Francesca Macchi, Samuele ... Dyk ned i forskningsemnerne om Wildtype and A30P Mutant Alpha-Synuclein Form Different Fibril Structures. Sammen danner de et ...
α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinsons disease (PD) as well as dementia ... Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem. 2009; ... Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein- ... 27. Borghi R, Marchese R, Negro A, Marinelli L, Forloni G, Zaccheo D, Abbruzzese G, Tabaton M. Full length alpha-synuclein is ...
alpha-Synuclein (alpha-Syn) is an intrinsically disordered protein which self-assembles into highly organized beta-sheet ... Structural Basis for Dityrosine-Mediated Inhibition of alpha-Synuclein Fibrillization. Research output: Contribution to journal ... Oxidative stress influences alpha-Syn structure and selfassembly; however, the basis for this remains unclear. Here we ... we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the alpha-Syn monomer ...
Neuropathological and phenotypic changes mediated by CK2α were connected to alpha-synuclein (α-syn) dysregulation and ... Yu, D., Zarate, N., White, A. et al. CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic ... CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in Huntingtons disease. ... CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in Huntingtons disease ...
... alpha-, beta-, and gamma-synuclein. All contain conserved alpha-helical lipid-binding motifs. ... The synuclein family consists of three small soluble proteins: ... Alpha Synuclein: Synuclein Family. Potential Targets in the ... The synucleins, additionally, seem to work together to uphold the PD phenotype42. Alpha synuclein is known to regulate dopamine ... Beta synuclein shares 60% sequence identity with alpha synuclein, however, it is not currently a primary target in PD therapy. ...
By STEVEN ZECOLA This study tracks the decades-long journey to harness alpha-synuclein as a treatment for Parkinsons disease. ... from the discovery of the effects of alpha-synuclein, the report stated that:. "New insights into the role of synucleins in the ... from the discovery of the effects of alpha-synuclein, the report stated that:. "New insights into the role of synucleins in the ... The Long and Tortured Past of Alpha-Synuclein & Parkinsons Disease By Debra Mitchell March 29, 2024 20 mins read 15 Views ...
Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinsons disease. ... Alpha-synuclein: pathology, peripheral expression, and environmental interactions. / Haikal, Caroline. Lund: Lund University, ... Alpha-synuclein: pathology, peripheral expression, and environmental interactions. Lund : Lund University, Faculty of Medicine ... Alpha-synuclein: pathology, peripheral expression, and environmental interactionsFinal published version, 13.4 MB ...
Alpha-synuclein119 aggregated more rapidly and enhanced significantly the fibril formation of alpha-synuclein. Although both of ... It is known that truncated alpha-synuclein has a much higher ability to aggregate and fibrillate than full-length alpha- ... alpha-synuclein133 showed a similar aggregation with full-length alpha-synuclein and no acceleration effect. We showed that PQQ ... synuclein. Since the fibrils and precursor oligomers of alpha-synuclein are cytotoxic to the neuron, inhibitors that prevent ...
Alpha-synuclein is a major component of Lewy body characteristic of PD and pathogenic mutation of α-synuclein is implicated in ... Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Exp Neurol. 2002;175(1 ... Mutation in the alpha-synuclein gene identified in families with Parkinsons disease. Science. 1997;276(5321):2045-2047 ... Synergistic effects of TDP-43 and mutant alpha-synuclein on dopaminergic neurons in transgenic mice. a-f, Double-fluorescence ...
Anti-Alpha Synuclein Antibody (pSer129) - 100 ul at 0.5mG./mL. https://www.cortex-biochem.com/shop/0400-spc-742d-a488-100ul- ... anti-alpha-synuclein-antibody-pser129-100-ul-at-0-5mg-ml-37497 https://www.cortex-biochem.com/web/image/product.template/37497/ ...
Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue ... Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain (2015) Erica L. Beatman et al. JOURNAL OF VIROLOGY The ... Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue Published 2022 View Full Article ... Alpha synuclein, the culprit in Parkinson disease, is required for normal immune function (2022) Md Masud Alam et al. Cell ...
Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinsons Disease.. PARNETTI, Lucilla;FAROTTI, LUCIA; ... CSF alpha synuclein (α-syn) species, namely total and oligomeric α-syn (t-α-syn and o-α-syn), have shown to be of help for PD ... CSF alpha synuclein (α-syn) species, namely total and oligomeric α-syn (t-α-syn and o-α-syn), have shown to be of help for PD ... study carried out in 44 PD patients and 25 neurological controls we wanted to verify whether the combination of CSF α-synuclein ...
Membrane binding, internalization, and sorting of alpha-synuclein in the cell Masaracchia C., Hnida M., Gerhardt E., Lopes da ...
When alpha-synuclein clumps develop in the brain, they are accompanied by activation of an immune response or inflammation. The ... Sunil Kumar: Preventing the Clumps of Alpha-synuclein. Dr. Sunil Kumar is an Assistant Professor in the Department of Chemistry ... His lab is now working to identify molecules that can bind to these sections of alpha-synuclein and interfere in its ... One of the fundamental questions underlying why PD occurs is: How does alpha-synuclein aggregate into these toxic clumps? ...
2000) Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in ... 2006) Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinsons models. Science 313:324-328. ... 2004) Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc Natl Acad Sci USA 101:14966-14971 ... 2006) Mechanisms of Parkinsons disease linked to pathological alpha-synuclein: new targets for drug discovery. Neuron 52:33-38 ...
The H50Q Mutation Enhances alpha-Synuclein Aggregation, Secretion, and Toxicity. O. Khalaf; B. Fauvet; A. Oueslati; I. Dikiy; A ... Effects of sedimentation, microgravity, hydrodynamic mixing and air-water interface on alpha-synuclein amyloid formation. J. ... Stable -Synuclein Oligomers Strongly Inhibit Chaperone Activity of the Hsp70 System by Weak Interactions with J-domain Co- ... Characterization of glycoprotein E C-End of West Nile virus and evaluation of its interaction force with alpha V beta 3 ...
  • Within these terminals, alpha-synuclein interacts with phospholipids and proteins. (wikipedia.org)
  • Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, making up as much as one percent of all proteins in the cytosol of brain cells. (wikipedia.org)
  • Highly selective and potent alpha-synuclein and tau imaging agents for PD and FTD can be used to non-invasively assess regional deposits of these proteins and to follow their removal with therapy. (michaeljfox.org)
  • Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins and organelles. (lu.se)
  • Yet, mice missing any one synuclein protein fail to exhibit improved dopamine levels and a change in the disease phenotype, perhaps due to the other synuclein proteins pathogenically compensating for the absence. (alpha-synuclein.net)
  • showed that alpha-synuclein (A-syn) was a major contributor of abnormal clusters of proteins in the brain, not only in patients with synuclein mutations but, more importantly, in patients with sporadic Parkinson's disease as well. (prohealthsciences.com)
  • TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. (ijbs.com)
  • Our finding provides in vivo evidence suggesting that disease proteins such as TDP-43 and α-synuclein may play a synergistic role in disease induction in neurodegenerative diseases. (ijbs.com)
  • Alpha-synuclein, present in mind cells, is made from amino acids like all proteins. (pianorc.com)
  • Neuropathological hallmarks of MSA are cell loss in the striatonigral and olivopontocerebellar structures of the brain and spinal cord accompanied by profuse, distinctive glia cytoplasmic inclusions (GCIs) formed by fibrillized alpha-synuclein proteins (defined as primary alpha-synucleinopathy). (medscape.com)
  • One similarity is that abnormal build-up of proteins occurs in both cases, accumulations of alpha-synuclein and beta-amyloid respectively. (lu.se)
  • In Parkinson's disease and other synucleinopathies, insoluble forms of alpha-synuclein accumulate as inclusions in Lewy bodies. (wikipedia.org)
  • Familial Parkinson's disease is associated with mutations in the -synuclein (SNCA) gene. (wikipedia.org)
  • Alpha synuclein potentially connects the gut-brain axis in Parkinson's disease patients. (wikipedia.org)
  • The presynaptic protein alpha-synuclein is considered to play an important role in the pathophysiology of Parkinson's disease (PD). (nih.gov)
  • Accumulation of alpha-synuclein and tau protein aggregates are pathological hallmarks of Parkinson's disease (PD) and Frontal Temporal Dementia (FTD), respectively. (michaeljfox.org)
  • Defects in the SNCA gene, which encodes alpha-synuclein, have been implicated in the pathogenesis of Parkinson's disease. (thermofisher.com)
  • Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive accumulation in selected neurons of protein inclusions containing alpha-synuclein and ubiquitin (5, 6). (2bscientific.com)
  • α-Synuclein aggregation is implicated in several neurodegenerative diseases, including Parkinson's disease (PD) and dementia with Lewy Bodies (DLB). (upenn.edu)
  • Preclinical reserpine models recapitulating motor and non-motor features of Parkinson's disease: Roles of epigenetic upregulation of alpha-synuclein and autophagy impairment. (iasp-pain.org)
  • Abnormal synuclein-alpha forms filamentous inclusions (Lewy bodies and Lewy neurites) in several neurodegenerative diseases, including Parkinson's disease (PD), dementia with Lewy bodies, and Alzheimer's disease. (neuromics.com)
  • α-synuclein (α-syn) aggregation can lead to degeneration of dopaminergic neurons in the substantia nigra pars compacta ( SNpc ) as invariably observed in patients with Parkinson's Disease (PD). (researchsquare.com)
  • α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. (aging-us.com)
  • Alpha synuclein (AS) is a highly studied protein that is related to many neurodegenerative diseases such as Parkinson's disease and a group of pathologies known as synucleinopathies. (saneurociencias.org.ar)
  • Mutations in alpha synuclein have been heavily associated with Parkinson's disease as the protein constitutes LBs and LNs. (alpha-synuclein.net)
  • The beta and gamma synuclein are not located in LBs or LNs, but they are linked to hippocampal axon pathology in Parkinson's disease 40 . (alpha-synuclein.net)
  • This study tracks the decades-long journey to harness alpha-synuclein as a treatment for Parkinson's disease. (prohealthsciences.com)
  • Parkinson's disease (PD) involves the selective damage of dopaminergic neuron cells resulting from the accumulation and fibril formation of alpha-synuclein. (biomedcentral.com)
  • While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. (ijbs.com)
  • In Parkinson's disease , alpha-synuclein (aSyn) forms insoluble Lewy bodies and Lewy neurites in brain neurons , and in type 2 diabetes , islet amyloid polypeptide (IAPP) comprises the amyloid in the islets of Langerhans . (bvsalud.org)
  • Head injury, alpha-synuclein Rep1, and Parkinson's disease. (cdc.gov)
  • Alpha-synuclein (aSyn) is a protein that, in humans, is encoded by the SNCA gene. (wikipedia.org)
  • Common inherited Parkinson disease is associated with mutations in the alpha-synuclein (SNCA) gene. (wikipedia.org)
  • Alpha-Synuclein (SNCA) is expressed predominantly in the brain, where it is concentrated in presynaptic nerve terminals (1). (2bscientific.com)
  • Scholars@Duke publication: Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain. (duke.edu)
  • Alpha-synuclein (SNCA) gene has been implicated in the development of rare forms of familial Parkinson disease (PD). (duke.edu)
  • The human alpha-synuclein protein is made of 140 amino acids. (wikipedia.org)
  • Therefore, NACP is now referred to as human alpha-synuclein. (wikipedia.org)
  • Binds within the 81-130 aa region of human alpha synuclein, determined using WB and ELISA with corresponding peptides. (thermofisher.com)
  • Aggregation in this model is induced by the intrastriatal injection of α-synuclein pre-formed fibrils and recapitulates several cardinal features of human PD, including progressive aggregation concomitant with dopaminergic degeneration and motor symptoms. (upenn.edu)
  • Additionally, the immunoproteasome degrades α-synuclein fibrils more efficiently than the constitutive proteasome. (upenn.edu)
  • Beta synuclein is fibril resistant under normal cytoplasmic conditions, however, the protein was reported to undergo a toxic gain of function mutation in response to changes in cytosolic pH and produce beta synuclein fibrils. (alpha-synuclein.net)
  • Since the fibrils and precursor oligomers of alpha-synuclein are cytotoxic to the neuron, inhibitors that prevent the formation of oligomers and/or fibrils might open the way to a novel therapeutic approach to PD. (biomedcentral.com)
  • Synuclein is a neuronal and glial cell protein that can aggregate into insoluble fibrils and form Lewy bodies. (msdmanuals.com)
  • To investigate this, we used quantitative proteomics to measure the relative abundance changes of the proteome and phosphoproteome in response to aggregation of endogenous α-synuclein in the brain of a mouse model. (upenn.edu)
  • The immunoproteasome, an altered form of the constitutive proteasome that is induced in response to stress, was elevated in response to α-synuclein aggregation. (upenn.edu)
  • In this study, we first characterized the aggregation and cytotoxicity of C-truncated alpha-synuclein119 and alpha-synuclein133 which have been found in both the normal and the pathogenic brain. (biomedcentral.com)
  • Although both of alpha-synuclein119 and alpha-synuclein133 showed a high cytotoxicity, alpha-synuclein133 showed a similar aggregation with full-length alpha-synuclein and no acceleration effect. (biomedcentral.com)
  • Point mutations in the alpha-synuclein gene have been demonstrated in familial PD and alpha-synuclein is a major component of Lewy bodies, the pathological hallmark of the sporadic disease. (nih.gov)
  • It is not clear whether abnormal accumulation of alpha-synuclein is the result of abnormal levels of expression of the gene in neurodegenerative conditions. (nih.gov)
  • Incubation of reserpine induced apoptosis, led to the accumulation of intracellular reactive oxygen species (ROS), lowered DNA methylation of alpha-synuclein gene, resulted in alpha-synuclein protein deposition, and elevated the ratio of LC3-II/LC3-Ⅰ and p62 in cultured SH-SY5Y cells. (iasp-pain.org)
  • The mechanistic studies showed that chronic reserpine exposure caused hypomethylation of the alpha-synuclein gene and up-regulated its expression and elevated the ratio of LC3-II/LC3-Ⅰ and expression of p62 in the substantia nigra of mice. (iasp-pain.org)
  • Mutations in the synuclein-alpha gene (A53T and A30P) have been reported in several families with autosomal dominant Parkinsonism. (neuromics.com)
  • Interestingly, concomitant overexpression of normal TDP-43 and mutant α-synuclein caused a more severe loss of dopaminergic neurons in the double transgenic mice as compared to single-gene transgenic mice. (ijbs.com)
  • While mutation in TDP-43 is linked to ALS and FTLD ( 17 - 21 ), mutation of the α-synuclein gene is associated with PD ( 22 - 26 ). (ijbs.com)
  • A new mutation has been reported, making a total of 15 different mutations that can cause premature stop codons in the alpha-L-iduronidase gene ( IDUA ), and the biochemistry of these mutations has been investigated. (medscape.com)
  • Recently, it has been shown that not only full-length alpha-synuclein, but also C-terminal truncated forms exist in the normal brain, as well as Lewy bodies, which are cytoplasmic inclusions in PD. (biomedcentral.com)
  • Alpha-synuclein staining of the pons of an MSA case showing the positive glial inclusions (40x). (medscape.com)
  • Tau-positive neuronal inclusions in neurons of the substantia nigra (no alpha synuclein-positive inclusions, as are found in Parkinson disease). (medscape.com)
  • It is known that truncated alpha-synuclein has a much higher ability to aggregate and fibrillate than full-length alpha-synuclein. (biomedcentral.com)
  • We showed that PQQ dramatically inhibits the fibril formation of C-terminal truncated alpha-synuclein110119, and 133 as well as the mixtures of full-length alpha-synuclein with these truncated variants. (biomedcentral.com)
  • The researchers took a portion of the protein or peptide from one finish of the alpha-synuclein protein strand and blended it with samples of the full-length alpha-synuclein protein. (pianorc.com)
  • New research has advanced our understanding of a protein called alpha-synuclein, which is believed to play a central role in damaging brain cells in Parkinson's. (parkinsons.org.uk)
  • LBD is associated with abnormal brain deposits of a protein called alpha-synuclein. (medlineplus.gov)
  • High levels of alpha-synuclein mRNA expression in neurons did not seem to be a marker for Lewy body formation. (nih.gov)
  • These findings are in broad agreement with other studies of the expression of alpha-synuclein mRNA in human brain and suggest that Lewy body formation is unlikely to be the result of overexpression of alpha-synuclein. (nih.gov)
  • The major neuropathological hallmarks of PD are intraneuronal accumulations of misfolded protein, which are termed Lewy bodies (LB) and Lewy neurites (LN). The main component of LBs and LNs is aggregated alpha-synuclein (α-syn) [ 1 ]. (aging-us.com)
  • The presence of cortical Lewy bodies is confirmed by the finding of alpha synuclein positive rounded cytoplasmic inclusion in neurons. (medscape.com)
  • In the brain, alpha-synuclein is found mainly in the axon terminals of presynaptic neurons. (wikipedia.org)
  • It has been established that alpha-synuclein is extensively localized in the nucleus of mammalian brain neurons, suggesting a role of alpha-synuclein in the nucleus. (wikipedia.org)
  • Synuclein is however found predominantly in the presynaptic termini, in both free or membrane-bound forms, with roughly 15% of synuclein being membrane-bound at any moment in neurons. (wikipedia.org)
  • Thus, it is suggested that alpha-synuclein in mitochondria is differentially expressed in different brain regions and the background levels of mitochondrial alpha-synuclein may be a potential factor affecting mitochondrial function and predisposing some neurons to degeneration. (wikipedia.org)
  • α-Synuclein (140 aa) is a natively unfolded protein that is enriched in the presynaptic terminal of the neurons in the brain. (biomedcentral.com)
  • TDP-43 potentiated α-synuclein toxicity to dopaminergic neurons in living animals. (ijbs.com)
  • To test this hypothesis, we examined whether TDP-43 potentiates α-synuclein toxicity to dopaminergic neurons in transgenic mice. (ijbs.com)
  • A lot of research has focused on developing treatments that can remove alpha-synuclein to see if this can help protect brain cells, and there are clinical trials of these experimental therapies underway. (parkinsons.org.uk)
  • Detection of alpha-synuclein and tau deposits in the brain of PD and FTD subjects would support early diagnosis and tracking disease progression, as well as the evaluation of drugs, currently under development, that target and remove alpha-synuclein and tau aggregates from the brain. (michaeljfox.org)
  • Some pesticides, such as the organophosphorus insecticide chlorpyrifos, appear to increase the expression of a-synuclein, a protein critically involved in Parkinson disease. (cdc.gov)
  • Alpha- and beta-synuclein have been shown to selectively inhibit phospholipase D2, suggesting that they may also be involved in signaling pathways. (thermofisher.com)
  • Beta synuclein shares 60% sequence identity with alpha synuclein, however, it is not currently a primary target in PD therapy. (alpha-synuclein.net)
  • At a pH of 5.8, beta synuclein fibrilization begins to occur 41 , which opens up the possibility of targeting beta synuclein in PD treatment. (alpha-synuclein.net)
  • An alpha-synuclein fragment, known as the non-amyloid beta (non-abeta) component (NAC) of Alzheimer's disease amyloid, originally found in an amyloid-enriched fraction, was shown to be a fragment of its precursor protein, NACP. (wikipedia.org)
  • It was later determined that NACP was the human homologue of Torpedo synuclein. (wikipedia.org)
  • Additionally, alpha-synuclein peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. (thermofisher.com)
  • Our results demonstrate that PQQ inhibits the amyloid fibril formation and cytotoxicity of the C-truncated alpha-synuclein variants. (biomedcentral.com)
  • Studies on alpha-synuclein and islet amyloid polypeptide interaction. (bvsalud.org)
  • An ability to visualize and quantify alpha-synuclein and tau aggregates in the brain would be valuable for diagnosing PD and FTD, accurately assessing disease stage and progression, and as a tool for evaluating drugs developed to treat these disorders. (michaeljfox.org)
  • Clearance and deposition of extracellular alpha-synuclein aggregates in microglia. (alzforum.org)
  • One of the key players in the development of the disease is the protein α-synuclein (aSN), which aggregates in the brain of PD patients. (au.dk)
  • A characteristic finding is cytoplasmic inclusion bodies containing alpha-synuclein within oligodendroglial cells. (msdmanuals.com)
  • Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release. (wikipedia.org)
  • It has also been shown that alpha-synuclein is localized in neuronal mitochondria. (wikipedia.org)
  • Alpha-synuclein119 aggregated more rapidly and enhanced significantly the fibril formation of alpha-synuclein. (biomedcentral.com)
  • Compounds that bind selectively to alpha-synuclein and tau deposits will be assessed using a variety of binding assays in test tubes. (michaeljfox.org)
  • Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. (ijbs.com)
  • Overexpression of pathogenically mutated α-synuclein causes dopaminergic neuron death in transgenic mice at advanced ages ( 34 ). (ijbs.com)
  • Expression of alpha-synuclein mRNA was therefore studied in control and PD brain using semiquantitative in situ hybridization. (nih.gov)
  • alpha-synuclein was expressed widely and hybridization signal was seen in most cortical regions, hippocampus, cerebellum, and brain stem. (nih.gov)
  • Interestingly, this research focused on the role of alpha-synuclein in healthy brain cells. (parkinsons.org.uk)
  • Alpha-synuclein is a protein that sticks together forming clumps within the brain cells affected in the condition. (parkinsons.org.uk)
  • But alpha-synuclein is also present in brain cells of people without Parkinson's. (parkinsons.org.uk)
  • This research studied healthy brain cells in the lab to explore some of the properties of alpha-synuclein. (parkinsons.org.uk)
  • The model showed that alpha-synuclein gathers on the inside surface of brain cells, where they connect with other cells. (parkinsons.org.uk)
  • Our research showed that this protein clings onto the inner face of the plasma membrane of brain cells so we are slowly building a picture of this very complex disorder by studying the key function of alpha-synuclein. (parkinsons.org.uk)
  • Western Blot analysis of Mouse, Rat Brain showing detection of 14 kDa Alpha Synuclein protein. (thermofisher.com)
  • A 1:1,000 dilution of MA5-45839 was sufficient for detection of Alpha Synuclein in 15 µg of human brain cell lysate by ECL immunoblot analysis using goat anti-mouse IgG:HRP as the secondary antibody. (thermofisher.com)
  • Alpha and beta are found mainly in the brain, while gamma is found in the peripheral nervous system. (alpha-synuclein.net)
  • In wholesome people, alpha-synuclein interacts with cell membranes, guaranteeing nerve cell communication. (pianorc.com)
  • The synucleins, additionally, seem to work together to uphold the PD phenotype 42 . (alpha-synuclein.net)
  • Additionally, in age-adjusted linear regression models for repeated measures, we assessed whether a-synuclein levels were associated with butyrylcholinesterase-chlorpyrifos adducts or cholinesterase inhibition measured in peripheral blood, or with self-reported pesticide exposure or paraoxonase (PON1) genotype. (cdc.gov)
  • In the process of seeded nucleation, alpha-synuclein acquires a cross-sheet structure similar to other amyloids. (wikipedia.org)
  • Alpha-synuclein is highly expressed in the mitochondria in olfactory bulb, hippocampus, striatum and thalamus, where the cytosolic alpha-synuclein is also rich. (wikipedia.org)
  • However, the cerebral cortex and cerebellum are two exceptions, which contain rich cytosolic alpha-synuclein but very low levels of mitochondrial alpha-synuclein. (wikipedia.org)
  • The following product was used in this experiment: alpha Synuclein Monoclonal Antibody (3C11), PerCP from Thermo Fisher Scientific, catalog # MA5-45839. (thermofisher.com)
  • Samples were incubated with Alpha Synuclein monoclonal antibody (Product # MA5-45839) at 1:1,000 for 2 hours at RT, followed by Goat Anti-Mouse HRP:IgG at 1:3,000 for 1 hour at RT. (thermofisher.com)
  • Methylation of alpha-synuclein in a Sudanese cohort. (cdc.gov)
  • One promising pathway is medication that may goal and disrupt alpha-synuclein dysfunction and forestall or gradual the development of a illness akin to Parkinson's. (pianorc.com)
  • We observed somewhat greater a-synuclein with the PON1-108T (lower paraoxonase enzyme) allele, and with = 10 h of exposure to cholinesterase inhibiting insecticides in the preceding 30 days, but neither of these associations followed a clear dose-response pattern. (cdc.gov)
  • It has been shown that alpha-synuclein is localized in the inner membrane of mitochondria, and that the inhibitory effect of alpha-synuclein on complex I activity of the mitochondrial respiratory chain is dose-dependent. (wikipedia.org)
  • These results suggest that selected genetic and environmental factors may affect a-synuclein blood levels. (cdc.gov)
  • 02 October 2023 - The anti-tangle molecule alpha-synuclein has been recognized by researchers from the College of Tub and Bristol to dam the tangles of a mind protein related to Parkinson's illness and different neurodegenerative illnesses that trigger dementia. (pianorc.com)
  • Moreover, PQQ decreases the cytotoxicity of truncated alpha-synuclein. (biomedcentral.com)
  • These lead compounds will be chemically modified and optimized to enhance their properties as potential positron emission tomography (PET) tracers for imaging alpha-synuclein and tau deposits in the brains of individuals with PD and FTD. (michaeljfox.org)
  • The long-term goal of this work is to produce radioactively labeled compounds for use in PET imaging studies to non-invasively assess alpha-synuclein and tau deposits in the brains of people with PD and FTD. (michaeljfox.org)