Citation

Hu J, Wang X. Front. Cell Neurosci. 2022; 15.

Copyright

(Copyright © 2022, Frontiers Research Foundation)

DOI

10.3389/fncel.2021.811852

PMID

unavailable

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide. With the increasing trend of population aging, the estimated number of AD continues to climb, causing enormous medical, social and economic burden to the society. Currently, no drug is available to cure the disease or slow down its progression. There is an urgent need to improve our understanding on the pathogenesis of AD and develop novel therapy to combat it. Despite the two well-known pathological hallmarks (extracellular amyloid plaques and intracellular Neurofibrillary Tangles), the exact mechanisms for selective degeneration and loss of neurons and synapses in AD remain to be elucidated. Cumulative studies have shown neuroinflammation plays a central role in pathogenesis of AD. Neuroinflammation is actively involved both in the onset and the subsequent progression of AD. Microglia are the central player in AD neuroinflammation. In this review, we first introduced the different theories proposed for the pathogenesis of AD, focusing on neuroinflammation, especially on microglia, systemic inflammation, and peripheral and central immune system crosstalk. We explored the possible mechanisms of action of stem cell therapy, which is the only treatment modality so far that has pleiotropic effects and can target multiple mechanisms in AD. Mesenchymal stem cells are currently the most widely used stem cell type in AD clinical trials. We summarized the ongoing major mesenchymal stem cell clinical trials in AD and showed how translational stem cell therapy is bridging the gap between basic science and clinical intervention in this devastating disorder. Copyright © 2022 Hu and Wang.

Language: en

Keywords

human; Review; quality of life; head injury; obesity; smoking; cognitive defect; environmental factor; Alzheimer disease; mental stress; daily life activity; disease exacerbation; hypercholesterolemia; hypertension; diabetes mellitus; vascular disease; interleukin 6; immunoglobulin enhancer binding protein; immune response; apolipoprotein E; protein phosphorylation; Mini Mental State Examination; brain derived neurotrophic factor; interleukin 10; astrocyte; neurofibrillary tangle; microglia; immunomodulation; reactive oxygen metabolite; natural killer cell; intestine flora; disorders of mitochondrial functions; randomized controlled trial (topic); mini international neuropsychiatric interview; synaptic transmission; somatomedin C; glial cell line derived neurotrophic factor; glial fibrillary acidic protein; nerve fiber degeneration; amyloid beta protein; tumor necrosis factor; interleukin 12; interleukin 13; transforming growth factor beta; tau protein; mesenchymal stem cell transplantation; alpha synuclein; phase 2 clinical trial (topic); vasculotropin; aquaporin 4; phase 1 clinical trial (topic); sedentary lifestyle; amyloid plaque; Alzheimer’s disease; Columbia suicide severity rating scale; nervous system inflammation; genome-wide association study; neuroinflammation; Clinical Dementia Rating; fecal microbiota transplantation; amyloid precursor protein; autophagia (mental disorder); CD33 antigen; chronic inflammatory response; clusterin; dysbiosis; mesenchymal stem cells; neurodegeneration; pathogenesis (nervous system); presenilin 1; presenilin 2; stem cell therapeutics; triggering receptor expressed on myeloid cells 2