Affiliation:
1. Science and innovation center, Guangzhou University of Chinese Medicine, Guangzhou, China
Abstract
Abstract:
The current studies show signs of progress in treating Alzheimer's disease (AD) with the
“brain-gut axis.” Restoring intestinal flora balance can alleviate neurodegeneration in the central
nervous system. However, due to the complex mechanisms involved in the brain-gut axis, the neuroprotective
mechanism brought by intestinal flora has not been fully understood. Trimethylamine
N-oxide (TMAO) is a microbiota-dependent metabolism production; TMAO has been proven to be
a major risk factor for atherosclerosis, thrombosis, type II diabetes, and other diseases. Meanwhile,
all the above diseases are associated with AD; thus, we speculate that TMAO and AD are also correlated.
Microbiota, such as Firmicutes, Ruminococcaceae, Escherichia coli, Bifidobacterium, Akkermansia,
etc., correlate with the production process of TMAO. High choline intake and insulin resistance
have also been identified as contributors to TMAO synthesis. With the increasing TMAO
in plasma, TMAO can enter the central nervous system, causing neuroinflammation and immune responses
and damaging the blood-brain barrier. TMAO can increase the expression of Aβ and the
hyperphosphorylation of tau protein, regulate the signal pathways of NLRP3/ASC/caspase1,
SIRT1/p53/p21/Rb, PERK/eIF2α/ER-stress, SIRT3-SOD2-mtROS, TXNIP-NLPR3, and
PERK/Akt/mTOR, and stimulate the inflammation, apoptosis, endoplasmic reticulum stress, and
the ROS. In this mini-review, we have summarized the diseases induced by TMAO through clinical
and signal pathways, and intestinal flora correlated with TMAO. Through the analysis of diseases
and mechanisms involved in TMAO, we have concluded TMAO to be a potentially important
pathological factor of AD.
Publisher
Bentham Science Publishers Ltd.
Subject
Cell Biology,Molecular Biology,Biochemistry,General Medicine