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The Role of Interferon-alpha in Neurodegenerative Diseases: A Systematic Review

Journal

JOURNAL OF ALZHEIMERS DISEASE
Volume 94, Issue -, Pages S45-S66

Publisher

IOS PRESS
DOI: 10.3233/JAD-221081

Keywords

Alzheimer's disease; amyotrophic lateral sclerosis; dementia; HIV-associated neurocognitive disorder; Huntington's disease; interferon-alpha; multiple sclerosis; Parkinson's disease

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Neurodegenerative diseases impose a significant burden on populations worldwide, and interferon-alpha (IFN-alpha) has been suggested as a potential therapeutic target for these diseases. However, the exact role of IFN-alpha in neurodegeneration remains unclear and requires further investigation.
Background: Neurodegenerative diseases (NDs) impose significant financial and healthcare burden on populations all over the world. The prevalence and incidence of NDs have been observed to increase dramatically with age. Hence, the number of reported cases is projected to increase in the future, as life spans continues to rise. Despite this, there is limited effective treatment against most NDs. Interferons (IFNs), a family of cytokines, have been suggested as a promising therapeutic target for NDs, particularly IFN-alpha, which governs various pathological pathways in different NDs. Objective: This systematic review aimed to critically appraise the currently available literature on the pathological role of IFN-alpha in neurodegeneration/NDs. Methods: Three databases, Scopus, PubMed, and Ovid Medline, were utilized for the literature search. Results: A total of 77 journal articles were selected for critical evaluation, based on the inclusion and exclusion criteria. The studies selected and elucidated in this current systematic review have showed that IFN-alpha may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-alpha may be displaying its neurotoxic function via various mechanisms such as abnormal calcium mineralization, activation of STAT1-dependent mechanisms, and increased quinolinic acid production. Conclusion: The exact role IFN-alpha in these neurodegenerative diseases have yet to be determine due to a lack in more recent evidence, thereby creating a variability in the role of IFN-alpha. Future investigations should thus be conducted, so that the role played by IFN-alpha in neurodegenerative diseases could be delineated.

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