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Review
. 2023 Feb 7:15:1100395.
doi: 10.3389/fnagi.2023.1100395. eCollection 2023.

Huntingtin-associated protein 1-associated intracellular trafficking in neurodegenerative diseases

Xingxing Chen  1   2 , Enhao He  1 , Chonglin Su  1 , Yan Zeng  1   2 , Jiang Xu  3
Affiliations
Review

Huntingtin-associated protein 1-associated intracellular trafficking in neurodegenerative diseases

Xingxing Chen et al. Front Aging Neurosci. .

Abstract

Huntingtin-associated protein 1 (HAP1), the first identified HTT-binding partner, is highly expressed in the central nervous system, and has been found to associated with neurological diseases. Mounting evidence suggests that HAP1 functions as a component of cargo-motor molecules to bind various proteins and participates in intracellular trafficking. It is known that the failure of intracellular transport is a key contributor to the progression of neurodegenerative disorders (NDs) including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), spinal and bulbar muscular atrophy (SBMA) and spinocerebellar ataxia (SCA). The link between HAP1 and various NDs is supported by growing evidence. This review aims to provide a comprehensive overview of the intracellular trafficking function of HAP1 and its involvement in NDs.

Keywords: Huntingtin-associated protein 1; aging; intracellular trafficking; neurodegenerative diseases; selective neurodegeneration.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The abnormal interaction of HAP1 with mutant HTT is an important contributor to the pathogenesis of neurodegeneration in HD. (A) HAP1 is involved in intracellular trafficking via its interaction with dynactin and kinesin. The dynactin complex promotes retrograde trafficking, while kinesin promotes anterograde trafficking. (B) HAP1-dependent intracellular trafficking important for neuronal functions is affected by the abnormal interaction of HAP1 with mutant HTT, therefore resulting in neurodegeneration in HD.
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