Abstract
Stem cell therapy improves memory loss and cognitive deficits in animal models with Alzheimer’s disease. The underlying mechanism remains to be determined, but it may involve the interaction of stem cells with hippocampal cells. The transplantation of stem cells alters the pathological state and establishes a novel balance based on multiple signaling pathways. The new balance mechanism is regulated by various autocrine and paracrine cytokines, including signal molecules that target (a) cell growth and death. Stem cell treatment stimulates neurogenesis and inhibits apoptosis, which is regulated by the crosstalk between apoptosis and autophagy—(b) Aβ and tau pathology. Aberrant Aβ plaques and neurofibrillary tau tangles are mitigated subsequent to stem cell intervention—(c) inflammation. Neuroinflammation in the lesion is relieved, which may be related to the microglial M1/M2 polarization—(d) immunoregulation. The transplanted stem cells modulate immune cells and shape the pathophysiological roles of immune-related genes such as TREM2, CR1, and CD33—(e) synaptogenesis. The functional reconstruction of synaptic connections can be promoted by stem cell therapy through multi-level signaling, such as autophagy, microglial activity, and remyelination. The regulation of new balance mechanism provides perspective and challenge for the treatment of Alzheimer’s disease.
Highlights
Departments of International Medical Service and of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Shuaifuyuan 1, Dong Cheng District, Chuan Qin and Yongning Li contributed to this article
Alzheimer’s disease (AD) is manifested with amyloid beta or β-amyloid (Aβ) peptide plaques, neurofibrillary tau tangles, neuronal death, synaptic alterations, and cerebral atrophy [1,2]
The expression of typical genes such as amyloid-beta precursor protein (APP), S182, STM-2 and APOE is linked with the pathogenesis of AD [7,8]
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by memory decline and cognitive impairment. Aberrant Aβ deposits and neurofibrillary tau aggregates induce neuronal death and synaptic loss Some genes such as APOE4, ABCA7 and SLC24A4 are related to cholesterol metabolism that is implicated with. Only a few medicines have certain effects, including (a) acetylcholinesterase inhibitors such as donepezil, galantamine, rivastigmine, and tacrine [18] They can compensate for the cholinergic decline by inhibiting acetylcholine turnover, (b) NMDA receptor antagonist memantine, and (c) Aβ-directed monoclonal antibody aducanumab. It is confirmed that the transplanted stem cells can repair cognitive impairment and improve behavioral performance in AD-like animal models as demonstrated by Morris water maze test, Y-maze alternation test, plus-maze discriminative avoidance task, social recognition test, and open-field evaluation [24,27,28]. AsAs a result, stem cellcell therapy alleviates neuropathology andand improves behavioral performance in animal mal models models withwith
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