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. 2023;94(s1):S45-S66.
doi: 10.3233/JAD-221081.

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

Brendan Su Mee Hui  1 , Lee Rui Zhi  1 , Thaarvena Retinasamy  2 , Alina Arulsamy  2 , Christine Shing Wei Law  3 , Mohd Farooq Shaikh  2   4   5 , Keng Yoon Yeong  3
Affiliations

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

Brendan Su Mee Hui et al. J Alzheimers Dis. 2023.

Abstract

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-α, 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-α 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-α may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-α 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-α 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-α. Future investigations should thus be conducted, so that the role played by IFN-α in neurodegenerative diseases could be delineated.

Keywords: Alzheimer’s disease; HIV-associated neurocognitive disorder; Huntington’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; dementia; interferon-alpha; multiple sclerosis.

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Conflict of interest statement

The authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
Type I IFNs, such as IFN-α, may bind to cell surface receptor containing two subunits: IFNAR1 and IFNAR2. This complex triggers the phosphorylation of the JAK-STAT proteins. The IFN regulatory factor 9 (IRF9), will form complexes with STAT dimers, and will translocate into the nucleus. Upon binding to interferon-sensitive response element (ISRE), IFN-induced genes would be expressed to induce IFN-mediated biological effects.
Fig. 2
Fig. 2
PRISMA flowchart showing article selection for systematic review.
Fig. 3
Fig. 3
Potential connections of IFN-α to different neurological disorders.
See this image and copyright information in PMC

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