• There are several types of surfactant dysfunction, which are identified by the genetic cause of the condition. (medlineplus.gov)
  • Chris' primary research focus is on using experimental and clinical data to predict how heart cells, the engine of every heartbeat, respond to genetic mutations and to drugs. (swansea.ac.uk)
  • The genetic alteration causative of SCAN-1 is a mutation altering the function of a gene called tdp1 (tyrosyl- DNA phosphodiesterase 1). (ataxia.org)
  • Using genetic as well as drug-like reagents, we will attempt to pinpoint potential therapeutic targets, and test whether manipulating these targets alleviates cellular defects in the context of LRRK2. (michaeljfox.org)
  • One of the challenges in designing genetic and cellular strategies is getting the therapy to the right place. (bioworld.com)
  • Our laboratory uses genetic, cell biological, and biochemical approaches to explore the pathogenesis of polyglutamine neurodegenerative diseases, the function of Math1 in neurodevelopment, and how MECP2 mutations cause postnatal neurodevelopmental disorders. (bcm.edu)
  • Mechanistic studies will determine how the MiT pathway links mitochondria-lysosomal dysfunctions in the disease cascade of PD in response to metabolic and genetic changes. (eurac.edu)
  • Sporadic" or non-inherited ALS, accounts for roughly 90% percent of cases, and 10% of cases are due to known genetic mutations. (bioquicknews.com)
  • But this study shows that 20 times that number have genetic mutations that could cause mitochondrial disease. (weeksmd.com)
  • however, direct etiological genetic and cellular evidence has thus far been lacking. (ox.ac.uk)
  • Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia. (ox.ac.uk)
  • Many factors can contribute to mitochondrial dysfunction including genetic mutations, aging, environmental factors, nutritional deficiencies, and metabolic disorders. (bmglabtech.com)
  • Many inherited diseases are caused by a genetic mutation that is present in every cell in the body, but causes dysfunction in only one tissue. (ubc.ca)
  • For example, a single mutation in the DNA sequence that codes for hemoglobin can result in sickle cell anemia, a genetic disorder that affects the shape and function of red blood cells. (atlasbars.com)
  • As with many neurodegenerative diseases, both rare autosomal-dominant forms of AD and more common sporadic forms with genetic risk factors without causative mutations exist. (medscape.com)
  • Despite the disparate pathogenesis of these two common forms of diabetes, they (along with secondary forms of diabetes resulting from genetic mutations or pharmaceutical or surgical interventions) all share microvascular injury/dysfunction as a chronic outcome. (medscape.com)
  • Setting aside sporadic mutations, every somatic cell in the body contains an identical genome with an identical complement of genes, each of which encodes a specific protein. (ernolaszlo.com)
  • HGPS is one of the laminopathies, caused by a (usually sporadic) mutation in the LMNA gene. (aad.org)
  • The article is titled "Nuclear Accumulation of CHMP7 Initiates Nuclear Pore Complex Injury and Subsequent TDP-43 Dysfunction in Sporadic and Familial ALS. (bioquicknews.com)
  • Patients with LRRK2 mutations exhibit a clinical and pathological phenotype indistinguishable from sporadic PD. (biomedcentral.com)
  • fAD-causing mutations in the genes coding for amyloid precursor protein ( APP ), presenilin 1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) affect the production of Aβ in the central nervous system (CNS), implicating altered APP cleavage and processing in the AD disease mechanism [ 1 ]. (nature.com)
  • Several mutations in the OCRL gene have been described, including truncation mutations, missense mutations, and large deletions. (medscape.com)
  • Mitochondria are small cellular constituents that generate cellular energy (ATP) by oxidative phosphorylation (OXPHOS). (nih.gov)
  • Mitochondria are the cellular powerhouse of eukaryotic cells, and they also regulate brain function through oxidative stress and apoptosis. (frontiersin.org)
  • Mitochondria could be targeted in the development of novel antidepressant drugs, and specific forms of mitochondrial dysfunction could be identified as biomarkers to personalize treatment and aid in early diagnosis by differentiating between disorders with overlapping symptoms. (frontiersin.org)
  • Those groups are not specifically targeting cellular senescence, but can hardly avoid having senescent cells taking up their therapeutic mitochondria. (fightaging.org)
  • Mitochondria provide and regulate cellular energy and are crucial for proper neuronal activity and survival. (scirp.org)
  • Additional processes in which mitochondria are involved include heat production, storage of calcium ions, calcium signaling, programmed cell death (apoptosis) and cellular proliferation. (justia.com)
  • US 20130022666 provides compositions comprising a lipid carrier and mitochondria as well as methods of delivering exogenous mitochondria to a cell and methods of treating or reversing progression of a disorder associated with mitochondrial dysfunction in a mammalian subject in need thereof. (justia.com)
  • Dysfunctions of mitochondria and the autophagy-lysosomal pathway (ALP) take part in the pathologic process of Parkinson's disease (PD) and are induced by most PD-associated mutations. (eurac.edu)
  • Mitotic segregation of mitochondria may result in asymmetric proportions of heteroplasmic allelic variants in descendant cellular lineages [ 5 ]. (biorxiv.org)
  • Altered mitochondrial dynamics, including excessive fission and fusion of mitochondria, also contribute to mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
  • We will dissect each step in the trafficking of proteins within neurons that carry LRRK2 mutations, with a focus on pathways that relate to the disposal of proteins. (michaeljfox.org)
  • The Abu-Remaileh Lab is interested in identifying novel pathways that enable cellular and organismal adaptation to metabolic stress and changes in environmental conditions. (stanford.edu)
  • The AAA-ATPase (ATPases associated with diverse cellular activities) valosin-containing protein (VCP), is essential for many cellular pathways including but not limited to endoplasmic reticulum-associated degradation (ERAD), DNA damage responses, and cell cycle regulation. (portlandpress.com)
  • Due to its abundance and versatile function, VCP participates in many cellular pathways including ERAD, endolysosomal trafficking, selective autophagy, cell cycle regulation, and DNA damage signaling [ 1 ]. (portlandpress.com)
  • These activities relate to NIH's AD+ADRD Research Implementation Milestone 2.N , "Clarify unique and converging cellular mechanisms related to tau pathogenesis, C9orf72 hexanucleotide repeat expansions, GRN mutations, and other targets and pathways contributing to FTD neurodegeneration. (nih.gov)
  • The three main pathways used to generate energy in eukaryotic organisms are glycolysis and the citric acid cycle/oxidative phosphorylation, both components of cellular respiration, and beta-oxidation. (justia.com)
  • Patients with PH exhibited higher circulating levels of microparticles compared to control subjects and in vitro or in vivo generated microparticles can induce endothelial dysfunction, interfere with coagulation pathways or modulate inflammatory phenomenon. (ersjournals.com)
  • The process of cell death involves several signaling pathways, including the autophagic-lysosomal pathway, intracellular trafficking, mitochondrial dysfunction, and the ubiquitin-proteasome system. (biomedcentral.com)
  • This statement reviews biochemical/cellular pathways involved in facilitating and abrogating microvascular injury. (medscape.com)
  • These mutations lead to a reduction in or absence of mature SP-B. In addition, SFTPB gene mutations cause abnormal processing of SP-C, resulting in a lack of mature SP-C and a buildup of unprocessed forms of SP-C. These changes lead to abnormal surfactant composition and decreased surfactant function. (medlineplus.gov)
  • Pathogenic mutations within each domain are indicated. (portlandpress.com)
  • The level of heteroplasmy of a pathogenic mtDNA mutation correlates with the severity of the clinical phenotype and mosaic distributions of mutations across an individual have been reported to lead to organ-specific dysfunction [ 4 ]. (biorxiv.org)
  • But today, the United Mitochondrial Disease Foundation announced a "landmark research finding" showing that at least one in 200 healthy humans "harbors a pathogenic mitochondrial mutation that potentially causes disease. (weeksmd.com)
  • Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10-4) mutations. (ox.ac.uk)
  • Structure of the functional domain of the LRRK2 protein and the pathogenic mutations associated with PD. (biomedcentral.com)
  • Spinocerebellar ataxia type 35 (SCA35) is a rare, autosomal dominant neurodegenerative disorder associated with mutations in TGM6 gene that encode the protein transglutaminase 6 (TG6). (ataxia.org)
  • Telomerase mutations cause autosomal dominant dyskeratosis congenita. (hopkinsmedicine.org)
  • Most cases of early-onset AD are linked to autosomal dominant inherited mutations in the genes encoding amyloid precursor protein ( APP ), presenilin 1 ( PSEN1 ), and presenilin 2 ( PSEN2 ). (biomedcentral.com)
  • The focus of this review is the link between mitochondrial dysfunction and major depression. (frontiersin.org)
  • In Parkinson's disease, a strong link between mitochondrial dysfunction and disease-associated genes has been documented. (bmglabtech.com)
  • A53T Mutation is a point mutation of the Alpha-synuclein protein, a 140-amino acid protein found in pre-synaptic terminals of neurons in the brain. (wikipedia.org)
  • Using five control induced pluripotent stem cell (iPSC) lines and seven iPSC lines generated from fAD patients, we investigated the effects of mutations on the Aβ secretome in human neurons generated in 2D and 3D. (nature.com)
  • Our previous studies of neurons with mutant LRRK2 kinase have pointed to defects in the cellular machinery that traffics cell-surface proteins towards a variety of intracellular destinations. (michaeljfox.org)
  • We hypothesize that LRRK2 mutations lead to PD due to inappropriate and defective trafficking of proteins between different compartments within neurons. (michaeljfox.org)
  • The goal of this work is to pinpoint the cellular trafficking defects in neurons that harbor LRRK2 mutations, and thus identify potential new drug targets. (michaeljfox.org)
  • Spinal muscular atrophy (SMA) is caused by mutations in the SMN1 gene, which encodes survival motor neuron 1, leading to reduced protein expression levels and degeneration of motor neurons in the spinal cord, with the consequent muscle atrophy. (bioworld.com)
  • To study how this mutation causes neurons to die, researchers created a new model that allows them to see the progression of events that leads to cell death. (nih.gov)
  • Then the researchers grew these stem cells into neurons and assembled those neurons into mini-brain models, looking for symptoms of cellular disease along the way. (nih.gov)
  • By studying lab-grown neurons derived from skin or blood cells from 10 normal controls, from 8 individuals with an ALS-causing mutation, and from 17 people with non-inherited ALS, researchers have found a possible starting point for the dysfunction that causes the disease. (bioquicknews.com)
  • We demonstrate that tissues prone to accumulating ΔmtDNA have lower mitophagy responses than those with low mutation levels, such as neurons. (biorxiv.org)
  • Together, these results suggest that PINK1 and parkin drive organism-wide patterns of heteroplasmy and provide evidence of a causal link between proteotoxicity, mitophagy, and mtDNA mutation levels in neurons. (biorxiv.org)
  • The close tie between mtDNA and cellular metabolic state also arises from the fact that mtDNA is highly subject to mutagenic attacks from reactive oxygen species released from the electron transport chain, leading to accumulation of somatic mutations. (northwestern.edu)
  • As each mitochondrion contains 2-10 copies of mtDNA and each cell contains hundreds to thousands copies, the presence of heterogeneous mtDNA sequences, due to different mutations in different copies, results in a condition called heteroplasmy. (northwestern.edu)
  • Increased levels of mtDNA heteroplasmy, as an indicator of cellular metabolic dysfunction, in turn leads to elevated metabolic abnormality due to amino acid coding change in key oxidative phosphorylation proteins. (northwestern.edu)
  • NUSeq provides mtDNA-seq for detection of specific mtDNA mutations associated with a disease, determination of mtDNA heteroplasmy, and haplogroup classification (Fig. 2). (northwestern.edu)
  • This hypothesis promotes mutations in mitochondrial DNA (mtDNA) as the basis for Alzheimer's disease. (scirp.org)
  • The mutations could lead to energy failure, increased oxidative stress, and accumulation of A β , which in a vicious cycle reinforces the mtDNA damage and oxidative stress. (scirp.org)
  • Mitochondrial dysfunction can be caused by a number of mechanisms including mtDNA deletions. (nature.com)
  • However, we still do not have a clear understanding of whether mtDNA mutations and subsequent mitochondrial dysfunction is involved in diabetic neuropathy. (nature.com)
  • In multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, however the mechanisms that drive these heteroplasmy differences are unknown. (biorxiv.org)
  • Mutations in the mtDNA that perturb the assembly of OXPHOS enzymes can cause devastating metabolic disorders [ 3 ]. (biorxiv.org)
  • The composition of the mitochondrial DNA (mtDNA) in each cell is in constant flux through processes of mutation, replication, and degradation. (biorxiv.org)
  • This leads to substrate accumulation in the lysosomes, cellular dysfunction and organ damage. (bioworld.com)
  • this process often begins with mutations that inactivate normal cellular mechanisms for monitoring the fidelity of DNA replication, resulting in the rapid accumulation of mutations in genes involved in controlling the growth and death of cells. (ernolaszlo.com)
  • Similarly, aging has long been known to be associated with the accumulation of mutations, leading to cellular dysfunction and, ultimately, to a senescent phenotype (Lee 2018). (ernolaszlo.com)
  • The mutation activates an alternative splice site, resulting in accumulation of an abnormal lamin A-derived protein named progerin. (aad.org)
  • The advent of next-generation DNA sequencing is accelerating our discovery of rare gene variants that may represent causative mutations in speech and language disorders. (mpi.nl)
  • The phospholipids and proteins that make up surfactant are packaged in cellular structures known as lamellar bodies. (medlineplus.gov)
  • These misfolded proteins may trigger a cellular response that results in cell damage and death. (medlineplus.gov)
  • Mutations in the genes that encode these proteins can result in disease. (cshl.edu)
  • Over the next few decades researchers would use SV40 replication to discover dozens of cellular proteins that are necessary for human cell genome replication. (cshl.edu)
  • Lysosomal function is critical for organismal homeostasis-mutations in genes encoding lysosomal proteins cause severe human disorders known as lysosomal storage diseases, and lysosome dysfunction is implicated in age-associated diseases including cancer, neurodegeneration and metabolic syndrome. (stanford.edu)
  • In this review, we summarize some of the latest knowledge on mitochondrial dysregulation in major depression (depicted in Figure 1 ) and also discuss how mitochondrial dysfunction could instigate downstream changes in extracellular matrix proteins such as reelin, neuronal nitric oxide (nNOS), oxidative stress, and inflammation, and finally adult hippocampal neurogenesis. (frontiersin.org)
  • We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. (hopkinsmedicine.org)
  • The Microphthalmia-associated Transcription Factor (MiT) family proteins (MITF, TFEB, TFE3, TFEC) are considered master regulators of autophagy and lysosomal biogenesis and their activity is regulated in response to nutrient availability, therefore connecting cellular metabolism with ALP function. (eurac.edu)
  • EQ`s mechanism of action was linked to its ability to inhibit the chaperon domain of Hsp90 thereby reducing the cellular levels of one of its client proteins, SF3B2 20 , 21 . (nature.com)
  • This can impair processes like mitochondrial transport and the clearance of proteins leading to bioenergetic deficits and neuronal dysfunction. (bmglabtech.com)
  • In humans and other life forms, proteins are encoded by the genome and interact with one another to perform normal cellular functions. (ubc.ca)
  • It enables cells to produce proteins, which are essential for various purposes such as cell signaling, cellular function, and DNA replication. (atlasbars.com)
  • Membrane trafficking defects caused by mutation in OCRL may explain renal tubular defects observed in Lowe syndrome, including the inability of proximal tubular cells (PTC) to reabsorb low-molecular weight (LMW) proteins and other solutes such as phosphorus and bicarbonate from the glomerular filtrate. (medscape.com)
  • This milder form of mitochondrial disorder, the doctors said, was probably caused by a mutation found in nuclear (as opposed to mitochondrial) DNA, and inherited through the father - rather than through the mother, as in classic mitochondrial disease. (weeksmd.com)
  • We found that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans . (biorxiv.org)
  • Study of these mutations offers a powerful way of interrogating key underlying disease mechanisms for all forms of AD [ 2 ]. (nature.com)
  • 2021). Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction. (mpi.nl)
  • In the last years several new mutations have been reported as associated to SCA35 but the mechanisms inducing neuronal degeneration are still uncovered. (ataxia.org)
  • Mutations cause ECM dysfunction by combinations of two mechanisms. (manchester.ac.uk)
  • Multiple System Atrophy (MSA) Multiple system atrophy is a relentlessly progressive neurodegenerative disorder causing pyramidal, cerebellar, and autonomic dysfunction. (msdmanuals.com)
  • Parkinson disease may share features of other synucleinopathies, such as autonomic dysfunction and dementia. (msdmanuals.com)
  • The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia. (helsinki.fi)
  • In the classic form, inherited mutations of mitochondrial DNA are passed down through the mother, causing a wide variety of pathologies, including seizures, digestive problems, paralysis, blindness, heart disease, neurodevelopmental disorders and other problems. (weeksmd.com)
  • Bone development and homeostasis are governed by a number of developmental signals, transcription factors and cellular metabolism. (duke.edu)
  • CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy. (helsinki.fi)
  • Protein post-translational modifications (PTMs) take many shapes, have many effects and are necessary for cellular homeostasis. (biologists.com)
  • This Review summarizes the more recent biochemical, cellular and mouse model studies that underscore the importance of the ER acetylation process in maintaining protein homeostasis and autophagy within the secretory pathway, and its impact on developmental and age-associated diseases. (biologists.com)
  • Other effects include impaired cellular respiration, altered cell signaling , apoptosis , and impaired calcium homeostasis . (bmglabtech.com)
  • Familial Alzheimer's disease (fAD) mutations alter amyloid precursor protein (APP) cleavage by γ-secretase, increasing the proportion of longer amyloidogenic amyloid-β (Aβ) peptides. (nature.com)
  • Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia. (ox.ac.uk)
  • These mutations result in a reduction or absence of mature SP-C and the buildup of abnormal forms of SP-C. It is unclear which of these outcomes causes the signs and symptoms of SP-C dysfunction. (medlineplus.gov)
  • abnormal cellular crosstalk can lead to the development of cancer and PH [ 4 , 5 ]. (ersjournals.com)
  • iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10-8), viability (P = 8.9 × 10-7), and myelination potential (P = 0.038). (ox.ac.uk)
  • This review focuses on the evidence supporting a clear association between amyloid- β toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage/death in Alzheimer's disease. (scirp.org)
  • F. Albrekkan and M. Kelly-Worden, "Mitochondrial Dysfunction and Alzheimer's Disease," Open Journal of Endocrine and Metabolic Diseases , Vol. 3 No. 2A, 2013, pp. 14-19. (scirp.org)
  • Several lines of evidence suggest the involvement of mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
  • Evidence also points to multiple genes being linked to mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
  • In this paper, we make the case that mitochondrial dysfunction could play an important role in the pathophysiology of depression. (frontiersin.org)
  • Although the exact role of cellular microparticles remains partially understood, there is increasing evidence to suggest an active role for microparticles in PH pathophysiology. (ersjournals.com)
  • This review summarizes the cellular function and pathophysiology of LRRK2 ROCO domain mutations in PD and the perspective of therapeutic approaches. (biomedcentral.com)
  • Whereas, distinct presenilin 1 ( PSEN1 ) mutations lead to either (2) reduced γ-secretase activity, (3) altered protein stability or (4) reduced PSEN1 maturation, all culminating in reduced γ-secretase carboxypeptidase-like activity. (nature.com)
  • Our goal is to understand how mutations in the gene LRRK2 can drive Parkinson's disease (PD) risk. (michaeljfox.org)
  • We have developed a variety of tools that aim not only at detailing the cellular defects associated with LRRK2 mutations, but also at determining whether we can rescue such defects using drug-like reagents. (michaeljfox.org)
  • Recent studies have shown that pathological mutations of LRRK2 can reduce the rate of guanosine triphosphate (GTP) hydrolysis, increase kinase activity and GTP binding activity, and subsequently cause cell death. (biomedcentral.com)
  • Alpha-synuclein has more than one known point-mutation, one being A53T where amino acid residue 53 is mutated from its native alanine to a threonine. (wikipedia.org)
  • Hannah does share the same single-point mutation in mitochondrial DNA as her mother, Terry. (weeksmd.com)
  • Accession I0040 Systematic name g.9771G>T, c.40G>T, r.40g>u, p.Val14Leu Original code patient Description A point mutation in the exon 2 leading to an amino acid Description change Date 12-May-2008 (Rel. (lu.se)
  • Accession I0041 Systematic name g.9900G>A, c.169G>A, r.169g>a, p.Glu57Lys Original code 1-SA Description A point mutation in the exon 2 leading to an amino acid Description change in the CC domain Date 13-May-2008 (Rel. (lu.se)
  • But this mutation is apparently benign (Terry Poling is just fine), is not described in the medical literature, and is not associated with any pathology at all. (weeksmd.com)
  • Role of the cystathionine β-synthase / H2S pathway in the development of cellular metabolic dysfunction and pseudohypoxia in down syndrome. (helsinki.fi)
  • This project aims at shedding light on a potential mechanistic role of the MiT transcription factor pathway in relation to cellular and mitochondrial health in the etiology of PD and seeks to identify novel targets with the capacity to upregulate the MiT pathway and to increase degradation of aggregates and defective organelles, which may serve as therapeutic approach. (eurac.edu)
  • Overall, this project will dissect the link between mitochondrial and ALP dysfunctions in PD and aim to exploit regulation of the MiT pathway as pharmacological target against PD and related neurodegenerative diseases. (eurac.edu)
  • Dysfunction of these organelles is linked to a heterogeneous group of multisystemic disorders, including diabetes, cancer, ageing-related pathologies and rare mitochondrial diseases. (nih.gov)
  • abstract = "Tissue-specific extracellular matrices (ECMs) are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited connective tissue disorders. (manchester.ac.uk)
  • Both Mitochondrial "disease" and "dysfunction" appear to be more common than previously thought - implications for autism, other disorders are "earth shattering. (weeksmd.com)
  • Shockingly, the nuclear DNA mutations that bring risk of dysfunction could be as common as 1-in-400 to 1-in-50 people - though no one knows how many people have developed actual mitochondrial disorders because of it. (weeksmd.com)
  • First, secretion of the mutated ECM components can be reduced by mutations affecting synthesis or by structural mutations causing cellular retention and/or degradation. (manchester.ac.uk)
  • Find out how microplate readers advance research into mitochondrial dysfunction and different neurodegenerative diseases. (bmglabtech.com)
  • In this blog, we look at the relationship between mitochondrial dysfunction and neurodegenerative disease. (bmglabtech.com)
  • Being reactive and unstable, free radicals attempt to steal electrons from neighboring cells which can disrupt normal cellular activity. (healthyayurveda.com)
  • Fabry disease is a metabolic disease characterized by a deficiency in the lysosomal α-galactosidase enzyme caused by mutations in the GLA gene. (bioworld.com)
  • Lysosomes are membrane-bound compartments that degrade macromolecules and clear damaged organelles to enable cellular adaptation to various metabolic states. (stanford.edu)
  • By developing novel tools and harnessing the power of metabolomics, proteomics and functional genomics, our lab will define 1) how the lysosome communicates with other cellular compartments to fulfill the metabolic demands of the cell under various metabolic states, 2) and how its dysfunction leads to rare and common human diseases. (stanford.edu)
  • We apply this knowledge to understand how lysosomal dysfunction leads to human diseases including neurodegeneration, cancer and metabolic syndrome. (stanford.edu)
  • Lowe syndrome is caused by an inherited mutation in the OCRL gene, mapped to chromosome Xq 26.1, which encodes the OCRL1 protein. (medscape.com)
  • Further, cellular senescence properties were improved by exogenous mitochondrial transplantation in oxidative stress -induced senescent ARPE-19 cells. (fightaging.org)
  • Mutations in the PINK1 gene (also known as PARK6) are associated with early onset Parkinson's disease. (bmglabtech.com)
  • However, the data in relation to antidepressant drug effects are contradictory: some studies reveal they have no effect on mitochondrial function or even potentiate dysfunction, whereas other studies show more beneficial effects. (frontiersin.org)
  • The RPE in AMD shows mitochondrial dysfunction suggesting an association of AMD with mitochondrial function. (fightaging.org)
  • The same authors have identified two emerging hallmarks, i.e., 'reprogramming of energy metabolism' and 'evading immune destruction', in 2011, and pointed out that all these hallmarks are enabled by two characteristics, i.e., 'genome instability and mutation' and 'tumor-promoting inflammation' [ 12 ]. (jcancer.org)
  • However, many disease-predisposing factors and/or contributing factors have been identified, including inflammation, endothelial cell dysfunction, aberrant vascular wall cell proliferation and mutations in the bone morphogenetic protein-receptor type 2 ( Bmpr2 ) gene [ 1 - 3 ]. (ersjournals.com)
  • Welding involves occupational exposure to an aerosol containing gases and metal-rich particulates that induce adverse physiological effects including inflammation, immunosuppression, and cardiovascular dysfunction. (cdc.gov)
  • With respect to the latter, mutations in subunit-encoding genes and assembly factors of the first OXPHOS complex (complex I) induce isolated complex I deficiency and Leigh syndrome. (nih.gov)
  • Some fraction of senescent cells become senescent for good reasons, such as potentially cancerous mutations or other forms of damage that produce dysfunction. (fightaging.org)
  • We also analysed matched CSF, post-mortem brain tissue, and iPSCs from the same participant with the APP V717I mutation. (nature.com)
  • These demonstrations of BBB dysfunction have been confirmed with biofluid biomarker data and observations of postmortem tissue analysis [ 6 , 12 - 17 ]. (hindawi.com)
  • This injury (and responses by the body directed toward its repair) cause tissue/organ dysfunction that affects the quality and duration of life for persons with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). (medscape.com)
  • 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. (hopkinsmedicine.org)
  • Mitochondrial dysfunction is evident in early stages of AD and is involved in AD pathogenesis. (scirp.org)
  • Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. (hopkinsmedicine.org)
  • ATP can be produced by a number of distinct cellular processes. (justia.com)
  • These well-regulated processes to transfer information between cells occur through direct cell-cell contact, various soluble bioactive factors and through cellular microparticles [ 6 , 7 ]. (ersjournals.com)
  • While the experiments in the current paper were in progress, Leavitt et al 7 provided in vivo evidence suggesting that wild type huntingtin can protect against the gain of function mutation caused by the expanded polyglutamine tract in mutant huntingtin, using a YAC transgenic mouse model. (bmj.com)
  • Preclinical validation of identified MiT activators to rescue PD-related phenotypic defects will be carried out in advanced cellular models and in vivo models of PD. (eurac.edu)
  • Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10-5). (ox.ac.uk)
  • Mutations in the nuclear DNA-encoded NDUFS4 gene, encoding the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) of complex I, induce 'mitochondrial complex I deficiency, nuclear type 1' (MC1DN1) and Leigh syndrome in paediatric patients. (nih.gov)
  • Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes. (uib.no)
  • Recently, mutations in the OCRL gene have also been identified with renal tubular reabsorption defects in a subset of patients with another X-linked disease called Dent-2 disease, characterized by LMW proteinuria, hypercalciuria, and nephrocalcinosis. (medscape.com)
  • Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. (jcancer.org)
  • While most researchers tend to overlook it because of its small size, the mitochondrial genome contains genes that are essential for cellular energetics and survival (Fig. 1). (northwestern.edu)
  • The signs and symptoms of surfactant dysfunction can vary in severity. (medlineplus.gov)
  • Other types, known as SP-C dysfunction and ABCA3 deficiency, have signs and symptoms that range from mild to severe. (medlineplus.gov)
  • The combination of SP-B and SP-C dysfunction may explain why the signs and symptoms of SP-B deficiency are so severe. (medlineplus.gov)
  • Moreover, cellular changes in the brain precede the first clinical symptoms by 10-15 years, and there is a lack of early diagnostic biomarkers for the prodromal stages of AD. (biomedcentral.com)
  • A mutation leading to substitution of a key amino acid in the prM protein of West Nile virus (WNV) occurred during persistent infection of an immunocompetent patient. (cdc.gov)
  • In this study, we isolated and sequenced WNV lineage 1 and identified an amino acid mutation in the prM protein sequence that occurred between day 19 and day 28 of persistent viremia and viruria in a person with confirmed WNV encephalitis. (cdc.gov)
  • CONCLUSIONS Our results suggest that wild type huntingtin can significantly reduce the cellular toxicity of mutant HD exon 1 fragments in both neuronal and non-neuronal cell lines. (bmj.com)
  • We were interested to test if wild type huntingtin protected against the toxicity of polyglutamine expansion mutations. (bmj.com)
  • These newer cell-based models hold great promise for deciphering how mutations in FOXP2, and other language-related genes, affect aspects of neuronal development such as proliferation, migration, neurite outgrowth, and plasticity. (mpi.nl)
  • This is because Drosophila genes controlling fundamental cellular functions, such as cell growth and death, are quite identical to those found in human cells. (ataxia.org)
  • On the single-cell level, lifespan has been shown to decrease in a logarithmic fashion as mutation burden increases (Lee 2018). (ernolaszlo.com)
  • Exogenous mitochondrial transplantation improved mitochondrial dysfunction and alleviated cellular senescence hallmarks, such as increased cell size, increased senescence-associated β-galactosidase activity, augmented NF-κB activity, increased inflammatory cytokines , and upregulated the cyclin-dependent kinase inhibitors p21 and p16 . (fightaging.org)
  • For example, if free radicals attack the cell membrane, enzymes, or even DNA this can produce a chain reaction of cellular destruction. (healthyayurveda.com)