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Review
. 2024 Jan 22;13(1):6.
doi: 10.1186/s40035-024-00398-w.

The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases

Arazu Sharif  1   2 , John Mamo  1   3 , Virginie Lam  1   4 , Hani Al-Salami  1   2 , Armin Mooranian  1   2 , Gerald F Watts  5 , Roger Clarnette  5 , Giuseppe Luna  2 , Ryu Takechi  6   7
Affiliations
Review

The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases

Arazu Sharif et al. Transl Neurodegener. .

Abstract

Neurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative stress, neuroinflammation and compromised blood-brain barrier (BBB) integrity. Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies. Emerging research indicates that probucol, a historic lipid-lowering medication, offers substantial potential in the realm of neurodegenerative disease prevention and treatment. Preclinical investigations have unveiled multifaceted cellular effects of probucol, showcasing its remarkable antioxidative and anti-inflammatory properties, its ability to fortify the BBB and its direct influence on neural preservation and adaptability. These diverse effects collectively translate into enhancements in both motor and cognitive functions. This review provides a comprehensive overview of recent findings highlighting the efficacy of probucol and probucol-related compounds in the context of various neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and cognitive impairment associated with diabetes.

Keywords: Amyloid-beta; Blood–brain barrier; Inflammation; Neurodegenerative disease; Oxidative stress; Probucol; Probucol analogues.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Schematic summary of the effects of probucol in protecting BBB (a), reducing oxidative stress (b), alleviating inflammation (c), and promoting neuronal survival and plasticity (d)
Fig. 2
Fig. 2
Chemical structures of probucol and probucol analogues
See this image and copyright information in PMC

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