BBMs play a crucial role in combating Alzheimer’s disease and should be prioritized. To embed them in routine primary care, it is essential for governments and health organizations to finance evaluations in varied demographics, establish coverage policies, and integrate BBMs into existing workflows. Their accuracy, comparable to traditional invasive methods, enables early detection of AD, allowing for lifestyle adjustments and therapies that may hinder or delay disease progression. For patients, this means gaining a sense of control, meeting their needs, and moving forward without the burden of an uncertain diagnosis. This is not merely a transient trend; embracing BBMs could fundamentally alter the perception of aging in a future where Alzheimer’s disease diminishes in prominence.
Muneeb Khawar, Pugazhandhi Bakthavatchalam· Nepal Journal of Epidemiolog...· 0 citations
BACKGROUND
Microglia, the resident immune cells of the central nervous system (CNS), maintain brain homeostasis and respond to pathological insults. Microglial dysfunction has been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Impaired lysosomal function, particularly defective lysosomal acidification, leads to the accumulation of undegraded material, thereby promoting neuroinflammation and neuronal damage.
PURPOSE
This review examines the mechanisms governing lysosomal acidification in microglia and evaluates its potential as both a therapeutic target and a prognostic biomarker in neurodegenerative diseases.
METHODS
The literature on microglial lysosomal acidification, lysosomal pH regulation, autophagy, and neurodegeneration was searched in PubMed, Scopus, and Web of Science. Relevant mechanistic, preclinical, and translational studies were critically appraised and synthesized.
RESULTS
Lysosomal acidification is increasingly recognized as a key regulator of microglial function and homeostasis. Defective acidification, driven by dysregulation of the vacuolar H+-ATPase (V-ATPase) proton pump, TFEB/TFE3 signaling pathways, and lysosomal ion channels such as TRPML1 and TMEM175, impairs autophagic flux and substrate degradation, facilitating the accumulation of neurotoxic aggregates including amyloid-β and α-synuclein. Emerging evidence suggests that the degree of microglial lysosomal acidification may serve as a prognostic biomarker for disease progression and therapeutic response. Restoration or enhancement of lysosomal acidification through pharmacological modulation of lysosomal pH, activation of autophagy, or targeting of key regulatory pathways has been shown to re-establish microglial homeostasis, attenuate neuroinflammation, and confer neuroprotection in preclinical models.
CONCLUSION
Restoration of microglial lysosomal acidification represents a promising therapeutic strategy for neurodegenerative diseases. A deeper understanding of the molecular mechanisms regulating lysosomal acidification in microglia may facilitate the identification of novel biomarkers and therapeutic targets, ultimately contributing to the development of innovative interventions for neurodegenerative disorders.
R. Jaganathan, Srilakshmi Vijayakumar, Yinchi Chen et al.· Neurobiology of Disease· 0 citations
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