期刊
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
卷 123, 期 -, 页码 238-256出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2021.01.015
关键词
Autophagy; Dopamine; Norepinephr i n e; Glutamate; Locus coeruleus; Stres s; Ventral tegmental Area; Neurodegeneration
资金
- Italian Ministry of Health, Ricerca Corrente 2020-2021
The catecholamine-containing brainstem nuclei LC and VTA are crucial for stress responses and may contribute to neurodegeneration, especially during chronic stress. Alterations in catecholamine systems can lead to cognitive decline and potentially increase the production of toxic dopamine and norepinephrine by-products, affecting proteostasis in various brain regions. The molecular events controlling neurotransmission, neuroplasticity, and proteostasis within LC and VTA impact different brain areas, with alterations in autophagy machinery within these nuclei potentially triggering early neurodegeneration.
The catecholamine-containing brainstem nuclei locus coeruleus (LC) and ventral tegmental area (VTA) are critically involved in stress responses. Alterations of catecholamine systems during chronic stress may contribute to neurodegeneration, including cognitive decline. Stress-related catecholamine alterations, while contributing to anxiety and depression, might accelerate neuronal degeneration by increasin g the formation of toxic dopamine and norepinephrine by-products. These, in turn, may impair proteostasis within a variety of cortical and subcortical areas. In particular, the molecular events governing neurotransmission, neuroplasticit y , and proteostasis within LC and VTA affect a variety of brain areas. Therefore, we focus on alterations of autophag y machinery in these nuclei as a relevant trigger in this chain of events. In fact, these catecholamine-containing areas are mostly prone to autophagy-dependent neurodegeneration. Thus, we propose a dynamic hypothesis according to which stress-induced autophagy alterations within the LC-VTA network foster a cascade towards early neurodegeneration within these nuclei.
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