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• W1991822016 abstract "Protein accumulation leads to CNS effects in Alzheimers disease, frontotemporal dementia, and other agerelated disorders. Common mechanisms may contribute to the progressive pathology in the different protein accumulation disorders, and synergistic toxicity between dissimilar protein structures may also be involved. Among several avenues being pursued to reduce proteins prone to oligomerization and/or aggregation, a lysosomal avenue has been described that regulates the lysosomal systems broad clearance capability. Lysosomes are the primary site for protein clearance, to remove old and misfolded proteins and maintain cellular homeostasis. Small-molecule lysosomal modulators trigger a feedback response in vitro and in vivo, resulting in marked up-regulation of cathepsins and other lysosomal enzymes without any indications of synaptic pathology, behavioral abnormalities, or major organ malfunctions. For the characterization and screening of lysosomal modulatory drugs, the hippocampal slice model of protein accumulation has proved very useful. The model exhibits experimentally-induced phosphorylated tau species, paired helical filament deposits, ubiquitinated inclusions, and protein oligomers, thus providing a valuable tool to study the associated sequelae underlying progressive cellular and synaptic compromise. In the absence of modulatory drugs, the protein accumulation events lead to microtubule destabilization, transport failure, and synaptic decline. When lysosomal modulators are administered to slices with pre-existing deposits, protein accumulations are reduced causing normalization of tau chemistry, restoration of tubulin structures and tubulin-binding proteins, and recovery of synaptic composition. Thus, positive modulators of the lysosomal system represent first-in-class drugs, providing a suitable strategy to enhance protein clearance, promote synaptic health, and slow the progression of proteinopathies. Keywords: Alzheimer's disease, Cathepsin, Hippocampal slice culture, Lysosomal enhancement, Lysosome modulation, PADK, Synaptic decline" @default.
• W1991822016 created "2016-06-24" @default.
• W1991822016 creator A5020704914 @default.
• W1991822016 date "2009-10-01" @default.
• W1991822016 modified "2023-09-28" @default.
• W1991822016 title "Lysosomal Modulatory Drugs for a Broad Strategy Against Protein Accumulation Disorders" @default.
• W1991822016 cites W125508901 @default.
• W1991822016 cites W1482580692 @default.
• W1991822016 cites W1488972347 @default.
• W1991822016 cites W1584834830 @default.
• W1991822016 cites W1691514701 @default.
• W1991822016 cites W1857306005 @default.
• W1991822016 cites W1964589079 @default.
• W1991822016 cites W1972312480 @default.
• W1991822016 cites W1975180009 @default.
• W1991822016 cites W1975860260 @default.
• W1991822016 cites W1976599886 @default.
• W1991822016 cites W1980323811 @default.
• W1991822016 cites W1981615019 @default.
• W1991822016 cites W1984073321 @default.
• W1991822016 cites W1984924722 @default.
• W1991822016 cites W1988022242 @default.
• W1991822016 cites W1990671250 @default.
• W1991822016 cites W1993465897 @default.
• W1991822016 cites W1993510408 @default.
• W1991822016 cites W1994997992 @default.
• W1991822016 cites W1997410519 @default.
• W1991822016 cites W1998750669 @default.
• W1991822016 cites W2002803690 @default.
• W1991822016 cites W2003130394 @default.
• W1991822016 cites W2003618511 @default.
• W1991822016 cites W2003887891 @default.
• W1991822016 cites W2004546493 @default.
• W1991822016 cites W2005069707 @default.
• W1991822016 cites W2007922488 @default.
• W1991822016 cites W2009434997 @default.
• W1991822016 cites W2012911738 @default.
• W1991822016 cites W2016496683 @default.
• W1991822016 cites W2026165513 @default.
• W1991822016 cites W2039428048 @default.
• W1991822016 cites W2039502252 @default.
• W1991822016 cites W2044846385 @default.
• W1991822016 cites W2044977537 @default.
• W1991822016 cites W2050293051 @default.
• W1991822016 cites W2053627364 @default.
• W1991822016 cites W2057249855 @default.
• W1991822016 cites W2058495283 @default.
• W1991822016 cites W2063236931 @default.
• W1991822016 cites W2067042124 @default.
• W1991822016 cites W2071561134 @default.
• W1991822016 cites W2073284047 @default.
• W1991822016 cites W2074040932 @default.
• W1991822016 cites W2075481535 @default.
• W1991822016 cites W2075875770 @default.
• W1991822016 cites W2076533476 @default.
• W1991822016 cites W2079054696 @default.
• W1991822016 cites W2079580304 @default.
• W1991822016 cites W2082006839 @default.
• W1991822016 cites W2083702866 @default.
• W1991822016 cites W2091173932 @default.
• W1991822016 cites W2093489701 @default.
• W1991822016 cites W2095380164 @default.
• W1991822016 cites W2096410114 @default.
• W1991822016 cites W2098306153 @default.
• W1991822016 cites W2099370040 @default.
• W1991822016 cites W2103477251 @default.
• W1991822016 cites W2106043356 @default.
• W1991822016 cites W2109727228 @default.
• W1991822016 cites W2117626437 @default.
• W1991822016 cites W2118265926 @default.
• W1991822016 cites W2118417727 @default.
• W1991822016 cites W2128779293 @default.
• W1991822016 cites W2130665305 @default.
• W1991822016 cites W2134334757 @default.
• W1991822016 cites W2148034814 @default.
• W1991822016 cites W2150999725 @default.
• W1991822016 cites W2152103960 @default.
• W1991822016 cites W2165021720 @default.
• W1991822016 cites W2166321762 @default.
• W1991822016 cites W2167937350 @default.
• W1991822016 cites W2171776741 @default.
• W1991822016 cites W2213203705 @default.
• W1991822016 cites W2263837564 @default.
• W1991822016 cites W2400556051 @default.
• W1991822016 doi "https://doi.org/10.2174/156720509789207903" @default.
• W1991822016 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19874268" @default.
• W1991822016 hasPublicationYear "2009" @default.
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