Will cellular immunotherapies end neurodegenerative diseases?

'Neuroinflammation', one of the hallmarks of many neurodegenerative diseases, causes inadvertent damage to neuronal tissue due to the immune system's response to the underlying pathology. The role of the immune system in the development and progression of many neurodegenerative diseases remains elusive, with conflicting evidence in similar model systems. Due to the complexity of the immune system's involvement and the limitations of preclinical models, indiscriminate targeting of any single immune cell population could lead to inadvertent effects in neurodegenerative disease. The concept of cellular immunotherapy and personalized immunotherapeutic approaches is becoming feasible with current technological advancements, and might provide a new avenue for treating neurodegenerative diseases. We draw a compelling analogy between the immune system's role in neurodegeneration and a construction crew, underscoring the potential of cellular immunotherapies (especially T cell-based) to remodel and repair the central nervous system (CNS). We advocate for the development of personalized immunotherapies that leverage advanced technologies such as single-cell V(D)J sequencing and chimeric antigen receptor T (CAR-T) cell therapy. These approaches could transform the immune system from an inadvertent enabler of neurodegeneration to a precise tool for restoring the CNS: a novel strategy to combat neurodegenerative diseases. Neurodegenerative disorders present major challenges to global health, exacerbated by an aging population and the absence of therapies. Despite diverse pathological manifestations, they share a common hallmark, loosely termed 'neuroinflammation'. The prevailing dogma is that the immune system is an active contributor to neurodegeneration; however, recent evidence challenges this. By analogy with road construction, which causes temporary closures and disruptions, the immune system's actions in the central nervous system (CNS) might initially appear destructive, and might even cause harm, while aiming to combat neurodegeneration. We propose that the application of cellular immunotherapies to coordinate the immune response towards remodeling might pave the way for new modes of tackling the roadblocks of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]