basmwklz OP t1_jdprb76 wrote on March 26, 2023 at 5:48 AM

Abstract: >Astrocytes provide key neuronal support, and their phenotypic transformation is implicated in neurodegenerative diseases. Metabolically, astrocytes possess low mitochondrial oxidative phosphorylation (OxPhos) activity, but its pathophysiological role in neurodegeneration remains unclear. Here, we show that the brain critically depends on astrocytic OxPhos to degrade fatty acids (FAs) and maintain lipid homeostasis. Aberrant astrocytic OxPhos induces lipid droplet (LD) accumulation followed by neurodegeneration that recapitulates key features of Alzheimer’s disease (AD), including synaptic loss, neuroinflammation, demyelination and cognitive impairment. Mechanistically, when FA load overwhelms astrocytic OxPhos capacity, elevated acetyl-CoA levels induce astrocyte reactivity by enhancing STAT3 acetylation and activation. Intercellularly, lipid-laden reactive astrocytes stimulate neuronal FA oxidation and oxidative stress, activate microglia through IL-3 signalling, and inhibit the biosynthesis of FAs and phospholipids required for myelin replenishment. Along with LD accumulation and impaired FA degradation manifested in an AD mouse model, we reveal a lipid-centric, AD-resembling mechanism by which astrocytic mitochondrial dysfunction progressively induces neuroinflammation and neurodegeneration.

derphurr t1_jdpuyrw wrote on March 26, 2023 at 6:36 AM

The transmission of OXPHOS disease and methods to prevent this ( 2005)

>Despite extensive studies on use of various pharmacological agents and vitamin supplements, there is still no cure for OXPHOS disease. Pharmacological therapy mainly relies on the administration of artificial electron acceptors, metabolites and cofactors or oxygen radical scavengers (Dimauro et al., 2004).

>Physical exercise can also be important to prevent disease manifestations. Most patients with mitochondrial disease are inactive because of exercise intolerance or fear for muscle damage, in spite of the fact that aerobic training increases work and oxidation capacity in these patients (Taivassalo et al., 2001; Taivassalo and Haller, 2004).