Modulation of BDNF/TrkB Signalling Pathway in Alzheimer's Disease: Mechanistic Insights and the Role of Stem Cell...

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by the accumulation of amyloid beta (aβ) plaques and neurofibrillary tangles, along with progressive deterioration of cognitive function. AD is the most common form of dementia and affects over 55 million people worldwide. Current treatments for AD are symptomatic-based rather than curative, which calls for the development of new therapeutic strategies. Stem cell therapy has shown promising results for neurodegenerative diseases, including AD. Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), and their downstream signalling cascades play crucial role in modulating neuronal survival, development and synaptic plasticity, which are vital for cognitive functioning, and this pathway is dysregulated in AD. While the BDNF/TrkB signalling pathway dysregulation and stem cell therapy are each widely studied in AD, the interplay between those two remains underexplored. This review focuses on the mechanistic insights of the BDNF/TrkB signalling pathway in normal physiological condition and AD, along with the effects of stem cell therapy on the pathway and its downstream cascades. The findings highlight the therapeutic outcomes in increasing BDNF/TrkB levels and functions, restoring synaptic plasticity, modulating downstream substrates activities and improving cognitive functions. In addition, challenges, limitations and future directions of stem cell therapy are discussed, underscoring the therapeutic benefits of this therapy for AD by modulating the BDNF/TrkB signalling pathway.