1. Autophagy status as a gateway for stress-induced catecholamine interplay in neurodegeneration.
- Author
-
Fornai, Francesco and Puglisi-Allegra, Stefano
- Subjects
- *
AUTOPHAGY , *NEURODEGENERATION , *LOCUS coeruleus , *CASCADE connections , *NORADRENALINE - Abstract
• LC-VTA connections are key in stress response and neurodegeneration. • Autophagy is key in the stress-related dysregulation of LC and VTA neurons. • VTA neuron loss may precede LC degeneration occurring in a pre-plaques phase in AD. • Early LC alterations may render VTA neurons more susceptible to neurodegeneration. • Autophagy alterations explain the differential progression of LC/VTA towards degeneration. 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 increasing 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, neuroplasticity, and proteostasis within LC and VTA affect a variety of brain areas. Therefore, we focus on alterations of autophagy 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF