Title:Energy Crisis Links to Autophagy and Ferroptosis in Alzheimer’s Disease:
Current Evidence and Future Avenues
Volume: 21
Issue: 1
Author(s): Da-Long He, Yong-Gang Fan*Zhan-You Wang*
Affiliation:
- Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province, Health Sciences Institute of China
Medical University, Shenyang, 110122, China
- Key Laboratory of Medical Cell Biology of Ministry of Education,
Health Sciences Institute of China Medical University, Shenyang, 110122, China
- Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province, Health Sciences Institute of China
Medical University, Shenyang, 110122, China
- Key Laboratory of Medical Cell Biology of Ministry of Education,
Health Sciences Institute of China Medical University, Shenyang, 110122, China
Keywords:
Alzheimer’s disease, energy crisis, autophagy, ferroptosis, iron metabolism, beta-amyloid, tau protein.
Abstract: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases
worldwide. The occult nature of the onset and the uncertainty of the etiology largely impede the development
of therapeutic strategies for AD. Previous studies revealed that the disorder of energy
metabolism in the brains of AD patients appears far earlier than the typical pathological features of
AD, suggesting a tight association between energy crisis and the onset of AD. Energy crisis in the
brain is known to be induced by the reductions in glucose uptake and utilization, which may be ascribed
to the diminished expressions of cerebral glucose transporters (GLUTs), insulin resistance,
mitochondrial dysfunctions, and lactate dysmetabolism. Notably, the energy sensors such as peroxisome
proliferators-activated receptor (PPAR), transcription factor EB (TFEB), and AMP-activated
protein kinase (AMPK) were shown to be the critical regulators of autophagy, which play important
roles in regulating beta-amyloid (Aβ) metabolism, tau phosphorylation, neuroinflammation, iron
dynamics, as well as ferroptosis. In this study, we summarized the current knowledge on the molecular
mechanisms involved in the energy dysmetabolism of AD and discussed the interplays existing
between energy crisis, autophagy, and ferroptosis. In addition, we highlighted the potential network
in which autophagy may serve as a bridge between energy crisis and ferroptosis in the progression
of AD. A deeper understanding of the relationship between energy dysmetabolism and AD may
provide new insight into developing strategies for treating AD; meanwhile, the energy crisis in the
progression of AD should gain more attention.