• These are 3-repeat tau-immunopositive bodies predominantly located in granular neurons in the hippocampal dentate gyrus, hippocampal CA1 pyramidal neurons, and layer II of frontal and temporal cortices. (medscape.com)
  • We used immunohistochemical and Western blot analysis to determine the distribution and amount of this protein in the frontal and temporal cortices of diseased and control subjects. (biomedcentral.com)
  • Pick disease is a taupathy, with accumulation of abnormal tau protein in the brain. (medscape.com)
  • Accumulation of abnormal protein leads to progressive neuronal dysfunction and loss. (medscape.com)
  • It may represent an accumulation of misfolded, damaged or unwanted proteins, awaiting or undergoing degradation. (biomedcentral.com)
  • The accumulation of misfolded proteins may adversely affect neuronal connectivity and plasticity and trigger cell death signalling pathways [ 2 ]. (biomedcentral.com)
  • Some neurodegenerative disorders that affect movement or memory have common molecular pathology, with accumulation of abnormal proteins (TDP-43 and Tau) in brain cells. (nih.gov)
  • Taupathies are syndromes that occur secondary to deposition of abnormal forms of tau protein in the brain. (medscape.com)
  • In FTD, nerve cells in the frontal and temporal lobes of the brain degenerate, causing changes in thinking, personality, and behavior. (nih.gov)
  • Unlike Alzheimer disease, which typically presents with impairment of recent memory associated with entorhinal cortex and hippocampal dysfunction, Pick disease typically affects the frontal and/or anterolateral temporal lobes. (medscape.com)
  • Clinically, the deficit appears restricted to the frontal and/or temporal lobes. (medscape.com)
  • These intracellular aggregations of misfolded proteins, such as the nuclear TAR DNA-binding protein of 43 kDa (TDP-43) that accumulates in the cytoplasm, are toxic to the affected neurons and are thought to contribute to neuronal cell death. (atlasantibodies.com)
  • Marked neuronal loss and cortical atrophy, especially in right ventral and dorsal frontal and anterior temporal regions. (medscape.com)
  • 6] Swollen (ballooned) neurons (Pick cells) and argentophilic neuronal inclusions, known as Pick bodies,[7] can disproportionally affect the frontal and temporal cortical regions. (medscape.com)
  • Valosin-containing protein (VCP, also p97, or Cdc48p in yeast) is an evolutionarily conserved, homo-hexameric, ubiquitin-selective, AAA-ATPase that functions in numerous ubiquitin-dependent protein quality control pathways. (portlandpress.com)
  • Valosin-containing protein (VCP) is an AAA+ ATPase that plays critical roles in multiple ubiquitin-dependent cellular processes. (bvsalud.org)
  • Our study demonstrates that TMEM106B protein abundance is increased with brain ageing in humans, establishes that dementia risk allele rs1990622-A predisposes to TMEM106B fibril formation in the hippocampus, and provides the first evidence that rs1990622-A affects brain lipid homeostasis, particularly myelin lipids. (biomedcentral.com)
  • The role of HSP27 in the pathogenesis of neurodegenerative disorders such as frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD) and motor neuron disease (MND) was investigated. (biomedcentral.com)
  • 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)
  • VCP primarily identifies ubiquitylated proteins in these pathways and mediates their unfolding and degradation by the 26S proteasome. (portlandpress.com)
  • VCP interacts with adaptor proteins to identify ubiquitylated substrates for degradation by the proteasome. (portlandpress.com)
  • Neurodegenerative diseases are commonly associated with the cytoplasmatic aggregation of misfolded proteins. (atlasantibodies.com)
  • Many neurodegenerative diseases are characterised by accumulations of misfolded proteins that can colocalise with chaperone proteins (for example, heat shock protein 27 (HSP27)), which might act as modulators of protein aggregation. (biomedcentral.com)
  • Chaperone proteins have therefore been implicated as potent modulators of protein conformational disorders, suppressing toxicity of misfolding proteins and modifying early events in the aggregation process in a cooperative and sequential manner reminiscent of their functions in de novo protein folding [ 5 ],[ 6 ]. (biomedcentral.com)
  • She employs human patient-derived induced pluripotent stem cells to elucidate the nuclear-cytoplasmic trafficking mechanisms in neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). (atlasantibodies.com)
  • Many neurodegenerative diseases, also termed as protein conformational diseases [ 1 ], are characterised by accumulations of misfolded proteins that often share morphological and biochemical features and can colocalise with several other proteins, including various chaperone proteins. (biomedcentral.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)
  • VCP identifies ubiquitylated substrates through numerous dedicated adaptor proteins and unfolds substrates by threading them through a central pore in the hexamer ( Figure 1 ). (portlandpress.com)
  • Tau protein is a highly soluble microtubule-associated protein (MAPT) and promotes microtubule polymerization and stabilization. (medscape.com)
  • Some anti-GPCR antibodies exist on the market, but the success rate of development is still poor compared with antibodies targeting soluble or peripherally anchored proteins. (awljournal.org)
  • Within this spectrum disease, we aim to understand at both cellular and molecular levels how a genetic mutation in the C9orf72 gene, which is the most common genetic cause of ALS/FTD to date, can lead to motor neuron loss and simultaneous forebrain cortical neuron loss. (atlasantibodies.com)
  • It functions as a molecular chaperone, aiding the refolding of non-native proteins, and plays a critical role in stabilisation of the cytoskeleton through interactions with several cytoskeletal components, such as actin, intermediate filaments and microtubules [ 7 ]. (biomedcentral.com)
  • Patients will be asked to donate blood or skin tissue for studies of genetic and cellular mechanisms of degeneration. (nih.gov)
  • Dysfunctional nuclear-cytoplasmic trafficking of RNA-binding proteins might contribute to neurological disorders. (atlasantibodies.com)
  • This family of disorders includes frontotemporal dementia (FTD), amytrophic lateral sclerosis (ALS), corticobasal syndrome (CBS), primary progressive aphasia (PPA) and progressive supranuclear palsy (PSP). (nih.gov)
  • Pick disease is one of the disorders classified under the term frontotemporal dementia (FTD). (medscape.com)
  • In a clinicopathologic series, only 5% of patients with clinically diagnosed frontotemporal dementia had classic Pick disease with Pick bodies at postmortem evaluation. (medscape.com)
  • As many as 50% of patients with frontotemporal dementia have a positive family history of dementia and inherit frontotemporal dementia as an autosomal dominant trait with high penetrance. (medscape.com)
  • Proteomic mass spectrometry permits the unbiased identification of cellular and biochemical changes in the brain as a function of ageing. (biomedcentral.com)
  • Various taupathies can be differentiated based on preferential areas of brain involvement and /or involvement of specific cells/cellular compartments. (medscape.com)
  • Tau protein in the brain is heterogeneous, due to alternative splice forms and post-translational modifications. (medscape.com)
  • Crowding of asymmetric proteins results in an asymmetric lateral pressure across the membrane which can be used by cells in a number of biological processes involving membrane remodeling. (portlandpress.com)
  • We performed in vitro functional studies and in silico modeling to investigate the impact of these variants on protein function. (bvsalud.org)
  • Developing affinity reagents recognizing and modulating G-protein coupled receptors (GPCR) function by traditional animal immunization or in vitro screening methods is challenging. (awljournal.org)
  • [ 7 ] can disproportionally affect the frontal and temporal cortical regions. (medscape.com)
  • The Parkinson's disease genes pink1 and parkin , which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. (sdbonline.org)
  • The increase in TMEM106B levels with ageing was specific to carriers of the rs1990622-A allele in the TMEM106B gene that increases risk for frontotemporal dementia, Alzheimer's disease, Parkinson's disease, and hippocampal sclerosis with ageing. (biomedcentral.com)
  • Cellular congestion is a highly complex problem as there is often no clear single root cause to tackle. (atlasantibodies.com)
  • A cellular transport disease is caused by defects at the nuclear pore complexes resulting in traffic jams at the cellular and nuclear membranes. (atlasantibodies.com)
  • Though previously considered rare, Picks disease is reported in up to 30% of frontotemporal dementia (FTLD)-tau autopsy cases. (medscape.com)