Metabolic Dysfunction of Astrocyte: An Initiating Factor in Beta-amyloid Pathology?
Astrocytes, the most important energy regulator in the brain, support brain energy needs. In the meantime, numerous studies have demonstrated that impaired brain glucose metabolism is closely linked to abnormal astrocytic metabolism in AD. Indeed, the interaction between amyloid plaques and perturbed astrocytic homeostasis contributes to AD pathogenesis and astrocytic metabolic dysfunction is thought to be a trigger for Aβpathology through oxidative stress and neuroinflammation Moreover, astrocytic metabolic dysfunction may regulate Aβgeneration via modulating proteolytic processing of amyloid precursor protein (APP) byβ-secretase,γ-secretase, andα-secretase, and may also modulate APP post-translational modifications such as glycosylation, phosphorylation, and tyrosine sulfation. While it is known that metabolic dysfunction of astrocytes contributes to the failure of Aβclearance, it has also been reported that such dysfunction has neuroprotective property and exhibits no detrimental outcomes. Therefore, the exact role of astrocytic metabolic dysfunction in Aβpathology remains to be further investigated.
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
Liang-Jun
LJ
Yan
Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Ming
M
Xiao
Department of Neurology, the Affiliated Hospital of Anhui Medical University, Lu'an People's Hospital. Wanxi W. 21, Lu'an, Anhui Province. China, 237005 Phone:+86-564-3338520.
Ran
R
Chen
Department of Neurology, the Affiliated Hospital of Anhui Medical University, Lu'an People's Hospital. Wanxi W. 21, Lu'an, Anhui Province. China, 237005 Phone:+86-564-3338520.
Zhiyou
Z
Cai
Alzheimer's disease; astrocytes; beta-amyloid protein; metabolic dysfunction