Protective effect of irisin against Alzheimer’s disease

Abstract

Despite being one of the greatest global challenges for health and social care in the 21st century, Alzheimer’s disease (AD) lacks specific medicine. Irisin, an exercise-generated muscle factor, emerges as a potential hormone for AD prevention and treatment because of its role in promoting the browning of white adipose tissue, accelerating energy expenditure, regulating energy metabolism, and improving insulin resistance. The study reviews classic hallmarks of AD and irisin’s physiology before discussing the possible mechanism by which irisin protects against AD in terms of its effects related to molecular biology and cellular biology. Results reveal that irisin sharpens learning memory by inducing the production of brain-derived neurotrophic factor (BDNF), lowers the production of inflammatory factors, protects neurology through astrocytes, and ameliorates AD symptoms by improving insulin resistance. The review aims to facilitate future experimental studies and clinical applications of irisin in preventing and treating AD.

Aerobic exercise, an effective prevention and treatment for mild cognitive impairment

“…Aerobic exercise promotes the secretion of exercise factors and hormonal molecules from peripheral tissues and organs (including skeletal muscle) to act on neurons in the brain directly or after modulating downstream proteins across the BBB. On the one hand, the entry of exercise factors into the brain promotes the secretion of neurotrophic factor (BDNF), increases synaptic plasticity, and has protective effects on neurons ( Chen et al, 2022 ). On the other hand, they improve the inflammatory environment and alleviate the inflammatory microenvironment in the brain ( Townsend et al, 2021 ).…”

“…Irisin is considered a motility inducer regulated by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which acts via the circulatory system in various parts of the body after shearing from precursor FNDC5 ( Kim et al, 2018 ). For example, irisin induces white fat browning and thermogenesis ( Chen et al, 2022 ). Interestingly, irisin can positively affect cognitive function in the brain through multiple pathways.…”

“…Aerobic exercise promoted PGC1-α expression via the AMPK and p38MAPK pathways, leading to increased irisin expression and, ultimately, positive effects on cognitive function. A study by Chen et al (2022) found that aerobic exercise increased irisin expression in the hippocampus and positively affected cognitive function. To demonstrate the relationship between irisin and cognitive impairment, Lourenco et al (2019) injected FNDC shRNA into the mouse brain, which impaired long-term hippocampal enhancement, markers of synaptic plasticity and cognitive function.…”

“…It crosses the BBB through the circulatory system into the central nervous system. It activates the cAMP/PKA/CREB and MAPK/ERK pathways, increasing BDNF in neurons ( Chen et al, 2022 ; Lu et al, 2023 ). Recent studies have found that the cAMP/PKA/CREB pathway can reduce the burden of neural tangles in the brain by inhibiting the transcription and expression of tau proteins ( Lu et al, 2023 ).…”

Irisin Levels in Cerebrospinal Fluid Correlate with Biomarkers and Clinical Dementia Scores in Alzheimer Disease

“…16 Considering these neuroprotective effects, 16 recently irisin has been investigated in the context of neurodegenerative diseases, including AD. 17,18 Notably, biological investigations and in silico systems suggested that the FNDC5/irisin system was able to interact with neuropathological features of AD as amyloid precursor protein, regulating the production of insoluble amyloid β (Aβ) and the formation of the senile extracellular plaques. 19 Interestingly, studies on mouse AD models revealed that the FNDC5/irisin levels were reduced in the hippocampus of mice that developed memory deficits, whereas the increase of the circulating and/or brain irisin levels increased the synaptic plasticity, improving memory and cognitive performance.…”