Abstract
Mitochondrial dysfunction is a hallmark of Parkinson’s disease (PD). Astrocytes are the most abundant glial cell type in the brain and are thought to play a pivotal role in the progression of PD. Emerging evidence suggests that many astrocytic functions, including glutamate metabolism, Ca2+ signaling, fatty acid metabolism, antioxidant production, and inflammation are dependent on healthy mitochondria. Here, we review how mitochondrial dysfunction impacts astrocytes, highlighting translational gaps and opening new questions for therapeutic development.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD) and the most common movement disorder worldwide (Dorsey et al, 2018)
While the majority of research investigating mitochondrial dysfunction in PD has been focused on neurons, recent studies suggest that mitochondrial dysfunction in astrocytes likely play a role in PD as well
Via betaoxidation, of oleic acid happens in astrocytic mitochondria and beta-oxidation in astrocytes is activated in model systems with elevated fatty acids (Ioannou et al, 2019), it is plausible that astrocytic mitochondria play a key role in mitigating the toxicity of α-syn in PD brains
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD) and the most common movement disorder worldwide (Dorsey et al, 2018). Recent genome-wide association studies (GWAS) have provided new genetic insights into the disease etiology, strengthening the possibility of specific gene variants playing a role in PD pathogenesis (Nalls et al, 2019). Mitochondrial Dysfunction in Astrocytes evidence suggests that PD is linked to combinatorial interactions between genetic risk factors, pathogens, exposure to environmental toxins, and aging. Astrocytes function to support neuronal homeostasis, participate in the maintenance of the blood–brain barrier (BBB), and are dynamic regulators of the neuronal synaptic communication and cerebral blood flow They provide continuous trophic support and energy metabolism to neurons by secreting glialderived neurotrophic factor (GDNF), regulating extracellular ion balance in the CNS, and shuttling lactate and glutamine to neurons (Sofroniew and Vinters, 2010). We discuss precisely how mitochondrial dysfunction in astrocytes may contribute to Parkinson’s disease and suggest new avenues for therapeutic development
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