What is the Impact of Thiamine Dyshomeostasis on Neurotrophic Signalling in HIV-Associated Neurodegeneration: A Systematic Review?
DOI:
https://doi.org/10.56778/rjhs.v4i1.773Keywords:
Brain-derived neurotrophic factor; HIV long-term survivors; Neurocognitive disorders; Peripheral nervous system diseases; Thiamine.Abstract
Human immunodeficiency virus-associated neurocognitive disorders and peripheral neuropathy remain persistent clinical challenges despite effective viral suppression through antiretroviral therapy. Recent evidence suggests that vitamin B1 dyshomeostasis serves as a critical metabolic bottleneck that accelerates axonal degeneration. This study aims to elucidate the molecular interplay between thiamine homeostasis and neurotrophic signaling in human immunodeficiency virus-associated neurodegeneration, specifically identifying metabolic drivers of axonal damage. Following the PRISMA 2020 guidelines, a comprehensive search was conducted across PubMed, Scopus, Web of Science, and Google Scholar for peer-reviewed studies published between 2018 and 2025. Quality assessment was performed using Joanna Briggs Institute tools to ensure high-quality evidence. The analysis revealed that viral proteins, particularly glycoprotein 120, disrupt solute carrier family 19 thiamine transporters, precipitating a mitochondrial adenosine triphosphate failure. This bioenergetic crisis fundamentally impairs the thiamine-neurotrophic axis by hindering the proteolytic cleavage of pro-brain-derived neurotrophic factor into its mature form and silencing the mitogen-activated protein kinase/extracellular signal-regulated kinase survival pathway, driving distal axonal degeneration. Conversely, interventions using high-dose thiamine and lipophilic derivatives, such as benfotiamine, effectively bypass transport barriers via passive diffusion, restore alpha-ketoglutarate dehydrogenase enzymatic activity, and suppress nuclear factor kappa B-mediated neuroinflammation, thereby stabilizing axonal integrity. In conclusion, thiamine dyshomeostasis represents a pivotal metabolic driver of neurodegeneration, and targeted supplementation with benfotiamine offers a promising therapeutic strategy to mitigate neurocognitive and peripheral deficits.
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