Matches in SemOpenAlex for { <https://semopenalex.org/work/W2888824643> ?p ?o ?g. }
- W2888824643 abstract "Lithium has long been used for the treatment of psychiatric disorders, due to its robust beneficial effect as a mood stabilizing drug. Lithium's effectiveness for improving neurological function is therefore well-described, stimulating the investigation of its potential use in several neurodegenerative conditions including Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD) diseases. A narrow therapeutic window for these effects, however, has led to concerted efforts to understand the molecular mechanisms of lithium action in the brain, in order to develop more selective treatments that harness its neuroprotective potential whilst limiting contraindications. Animal models have proven pivotal in these studies, with lithium displaying advantageous effects on behavior across species, including worms (C. elegans), zebrafish (Danio rerio), fruit flies (Drosophila melanogaster) and rodents. Due to their susceptibility to genetic manipulation, functional genomic analyses in these model organisms have provided evidence for the main molecular determinants of lithium action, including inhibition of inositol monophosphatase (IMPA) and glycogen synthase kinase-3 (GSK-3). Accumulating pre-clinical evidence has indeed provided a basis for research into the therapeutic use of lithium for the treatment of dementia, an area of medical priority due to its increasing global impact and lack of disease-modifying drugs. Although lithium has been extensively described to prevent AD-associated amyloid and tau pathologies, this review article will focus on generic mechanisms by which lithium preserves neuronal function and improves memory in animal models of dementia. Of these, evidence from worms, flies and mice points to GSK-3 as the most robust mediator of lithium's neuro-protective effect, but it's interaction with downstream pathways, including Wnt/β-catenin, CREB/brain-derived neurotrophic factor (BDNF), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and toll-like receptor 4 (TLR4)/nuclear factor-κB (NFκB), have identified multiple targets for development of drugs which harness lithium's neurogenic, cytoprotective, synaptic maintenance, anti-oxidant, anti-inflammatory and protein homeostasis properties, in addition to more potent and selective GSK-3 inhibitors. Lithium, therefore, has advantages as a multi-functional therapy to combat the complex molecular pathology of dementia. Animal studies will be vital, however, for comparative analyses to determine which of these defense mechanisms are most required to slow-down cognitive decline in dementia, and whether combination therapies can synergize systems to exploit lithium's neuro-protective power while avoiding deleterious toxicity." @default.
- W2888824643 created "2018-09-07" @default.
- W2888824643 creator A5005678634 @default.
- W2888824643 creator A5009826322 @default.
- W2888824643 creator A5090756539 @default.
- W2888824643 date "2018-08-28" @default.
- W2888824643 modified "2023-10-16" @default.
- W2888824643 title "Molecular Mechanisms of Lithium Action: Switching the Light on Multiple Targets for Dementia Using Animal Models" @default.
- W2888824643 cites W1492443634 @default.
- W2888824643 cites W1505414983 @default.
- W2888824643 cites W1522284801 @default.
- W2888824643 cites W1527750088 @default.
- W2888824643 cites W1565087407 @default.
- W2888824643 cites W1567624342 @default.
- W2888824643 cites W1584771014 @default.
- W2888824643 cites W1599930612 @default.
- W2888824643 cites W1606139855 @default.
- W2888824643 cites W1963504172 @default.
- W2888824643 cites W1968117010 @default.
- W2888824643 cites W1969942100 @default.
- W2888824643 cites W1973257468 @default.
- W2888824643 cites W1973991760 @default.
- W2888824643 cites W1974808515 @default.
- W2888824643 cites W1975257189 @default.
- W2888824643 cites W1978494744 @default.
- W2888824643 cites W1980166477 @default.
- W2888824643 cites W1985124617 @default.
- W2888824643 cites W1985621776 @default.
- W2888824643 cites W1987264999 @default.
- W2888824643 cites W1989385223 @default.
- W2888824643 cites W1989723790 @default.
- W2888824643 cites W1989787517 @default.
- W2888824643 cites W1991856249 @default.
- W2888824643 cites W1993473208 @default.
- W2888824643 cites W1994567019 @default.
- W2888824643 cites W1995058974 @default.
- W2888824643 cites W2000209446 @default.
- W2888824643 cites W2000324903 @default.
- W2888824643 cites W2000547390 @default.
- W2888824643 cites W2002636911 @default.
- W2888824643 cites W2004855983 @default.
- W2888824643 cites W2005504181 @default.
- W2888824643 cites W2006733352 @default.
- W2888824643 cites W2007188652 @default.
- W2888824643 cites W2013316180 @default.
- W2888824643 cites W2016794759 @default.
- W2888824643 cites W2017197221 @default.
- W2888824643 cites W2017608412 @default.
- W2888824643 cites W2019093755 @default.
- W2888824643 cites W2019172653 @default.
- W2888824643 cites W2019495983 @default.
- W2888824643 cites W2020291601 @default.
- W2888824643 cites W2020311418 @default.
- W2888824643 cites W2020815630 @default.
- W2888824643 cites W2022603716 @default.
- W2888824643 cites W2022812113 @default.
- W2888824643 cites W2023167817 @default.
- W2888824643 cites W2023239280 @default.
- W2888824643 cites W2024486446 @default.
- W2888824643 cites W2024493236 @default.
- W2888824643 cites W2025565849 @default.
- W2888824643 cites W2025998453 @default.
- W2888824643 cites W2029582543 @default.
- W2888824643 cites W2030437631 @default.
- W2888824643 cites W2031785254 @default.
- W2888824643 cites W2034268376 @default.
- W2888824643 cites W2034703986 @default.
- W2888824643 cites W2036093656 @default.
- W2888824643 cites W2036225615 @default.
- W2888824643 cites W2037426713 @default.
- W2888824643 cites W2037653131 @default.
- W2888824643 cites W2039229967 @default.
- W2888824643 cites W2039873727 @default.
- W2888824643 cites W2040316712 @default.
- W2888824643 cites W2043606146 @default.
- W2888824643 cites W2045160140 @default.
- W2888824643 cites W2046129143 @default.
- W2888824643 cites W2047944478 @default.
- W2888824643 cites W2049146362 @default.
- W2888824643 cites W2051788298 @default.
- W2888824643 cites W2054780831 @default.
- W2888824643 cites W2055285423 @default.
- W2888824643 cites W2055387879 @default.
- W2888824643 cites W2057327606 @default.
- W2888824643 cites W2058227131 @default.
- W2888824643 cites W2059051998 @default.
- W2888824643 cites W2061342941 @default.
- W2888824643 cites W2064587868 @default.
- W2888824643 cites W2065247147 @default.
- W2888824643 cites W2067176728 @default.
- W2888824643 cites W2067311816 @default.
- W2888824643 cites W2070350114 @default.
- W2888824643 cites W2071075776 @default.
- W2888824643 cites W2073264699 @default.
- W2888824643 cites W2073505451 @default.
- W2888824643 cites W2077464456 @default.
- W2888824643 cites W2078246734 @default.
- W2888824643 cites W2079297432 @default.
- W2888824643 cites W2079462073 @default.
- W2888824643 cites W2079835998 @default.