Journal of Alzheimer's disease : JAD · 2023
Hippocampal Reduction of α-Synuclein via RNA Interference Improves Neuropathology in Alzheimer's Disease Mice.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Leitão André D G, Spencer Brian, Sarsoza Floyd, Ngolab Jennifer, Amalraj Jessica, Masliah Eliezer, Wu Chengbiao, Rissman Robert A
Аннотация
BACKGROUND: Alzheimer's disease (AD) cases are often characterized by the pathological accumulation of α-synuclein (α-syn) in addition to amyloid-β (Aβ) and tau hallmarks. The role of α-syn has been extensively studied in synucleinopathy disorders, but less so in AD. Recent studies have shown that α-syn may also play a role in AD and its downregulation may be protective against the toxic effects of Aβ accumulation.
OBJECTIVE: We hypothesized that selectively knocking down α-syn via RNA interference improves the neuropathological and biochemical findings in AD mice.
METHODS: Here we used amyloid precursor protein transgenic (APP-Tg) mice to model AD and explore pathologic and behavioral phenotypes with knockdown of α-syn using RNA interference. We selectively reduced α-syn levels by stereotaxic bilateral injection of either LV-shRNA α-syn or LV-shRNA-luc (control) into the hippocampus of AD mice.
RESULTS: We found that downregulation of α-syn results in significant reduction in the number of Aβ plaques. In addition, mice treated with LV-shRNA α-syn had amelioration of abnormal microglial activation (Iba1) and astrocytosis (GFAP) phenotypes in AD mice.
CONCLUSION: Our data suggests a novel link between Aβ and α-syn pathology as well as a new therapeutic angle for targeting AD.
OBJECTIVE: We hypothesized that selectively knocking down α-syn via RNA interference improves the neuropathological and biochemical findings in AD mice.
METHODS: Here we used amyloid precursor protein transgenic (APP-Tg) mice to model AD and explore pathologic and behavioral phenotypes with knockdown of α-syn using RNA interference. We selectively reduced α-syn levels by stereotaxic bilateral injection of either LV-shRNA α-syn or LV-shRNA-luc (control) into the hippocampus of AD mice.
RESULTS: We found that downregulation of α-syn results in significant reduction in the number of Aβ plaques. In addition, mice treated with LV-shRNA α-syn had amelioration of abnormal microglial activation (Iba1) and astrocytosis (GFAP) phenotypes in AD mice.
CONCLUSION: Our data suggests a novel link between Aβ and α-syn pathology as well as a new therapeutic angle for targeting AD.