TL;DR
It is proposed that the α-synuclein pathology starts in the gut with the non-motor symptoms, and then it propagates to the brain via the vagus nerve causing motor symptoms, which has emerged as an attractive target for immunotherapies.
New knowledge about the protective and detrimental aspects of neuroinflammation in AD and PD is summarized, providing an analysis on these developing prospects for targeted interventions toward slowing or stopping neurodegeneration.
Natural bioactive compounds, gene-based therapies, stem cell-based therapies, stem cell-based therapies, and nanotechnology-assisted drug delivery systems are promising alternatives as suggested by recent advances and could help to more effectively and permanently manage PD.
The protective and deleterious roles of NETs are investigated and how this knowledge may reveal new therapeutic strategies to modulate neurodegenerative diseases and preserve neural integrity are investigated, offering valuable insights for potential applications in clinical practice.
Neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and post-stroke sequelae, and rare disorders, including amyotrophic lateral sclerosis and multiple system atrophy, are characterized by complex neuroinflammatory processes and pathogenic protein aggregation. Natural killer and γδT cells, as pivotal immune effector cells, possess unique immunoregulatory and pathologic protein clearance capabilities, making these cells promising candidates for adoptive immunotherapy strategies. This review comprehensively discusses the synergistic mechanisms by which natural killer and γδT cells cross the blood-brain barrier and eliminate pathogenic proteins. Moreover, the mechanisms by which these cells modulate neuroinflammation and eliminate autoreactive T cells in the central nervous system are elucidated. The multifaceted roles across various neurodegenerative conditions are explored and the potential for clinical translation is evaluated. This review aims to provide theoretical and practical guidance for the development of innovative immune cell-based therapies targeting neurodegenerative diseases by integrating current research advances and identifying existing challenges.
