期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 193, 期 -, 页码 134-157出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2022.09.032
关键词
Alzheimer?s disease (AD); Dementia; Diabetes; Glucose metabolism; Insulin signaling; Mitochondrial dysfunction; Neurodegenerative diseases
资金
- Council of Scientific and Industrial Research, New Delhi, India [02(0275)/16/EMR-II]
- State government Research Fellowship [R-11/13/20]
- Ramalingaswami Fellowship
- DBT, India [BT/RLF/Reentry/22/2016]
- Kakatiya Medical College, Warangal [102/IFD/SAN/1117/2018-19]
- CSIR-IICT Hyderabad
- DBT [BT/PR35841/MED/32/745/2020]
- NIH [R01AG042178, R01AG47812, R01NS105473, AG060767, AG069333, AG066347]
This article systematically evaluates the abnormal glucose metabolism associated with amyloid beta and phosphorylated tau accumulation in AD, and discusses the role of insulin signaling and mitochondrial dysfunction in the progression of AD pathology.
Increasing evidence suggests that abnormal cerebral glucose metabolism is largely present in Alzheimer's disease (AD). The brain utilizes glucose as its main energy source and a decline in its metabolism directly reflects on brain function. Weighing on recent evidence, here we systematically assessed the aberrant glucose metabolism associated with amyloid beta and phosphorylated tau accumulation in AD brain. Interlink between insulin signaling and AD highlighted the involvement of the IRS/PI3K/Akt/AMPK signaling, and GLUTs in the disease progression. While shedding light on the mitochondrial dysfunction in the defective glucose metabolism, we further assessed functional consequences of AGEs (advanced glycation end products) accumulation, polyol activation, and other contributing factors including terminal respiration, ROS (reactive oxygen species), mito-chondrial permeability, PINK1/parkin defects, lysosome-mitochondrial crosstalk, and autophagy/mitophagy. Combined with the classic plaque and tangle pathologies, glucose hypometabolism with acquired insulin resis-tance and mitochondrial dysfunction potentiate these factors to exacerbate AD pathology. To this end, we further reviewed AD and DM (diabetes mellitus) crosstalk in disease progression. Taken together, the present work discusses the emerging role of altered glucose metabolism, contributing impact of insulin signaling, and mito-chondrial dysfunction in the defective cerebral glucose utilization in AD.
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