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

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.

Multifunctional Liposomes Targeting Amyloid‐β Oligomers for Early Diagnosis and Therapy of Alzheimer's Disease

“…However, the clearance of Cy5‐CP‐2‐LPs from the brains of 5xFAD mice was significantly slower compared to WT mice ( p <0.05), leading to their accumulation in the brain. Although the precise mechanism behind the prolonged retention of Cy5‐CP‐2‐LPs in the brain of 5xFAD mice is still under investigation, it may be attributed to the compromised BBB in this AD model [ 73 ] or, more likely, to the binding of Cy5‐CP‐2‐LPs to Aβ species in the brains of 5xFAD mice, enabling the effective visualization of amyloid species in the young transgenic 5xFAD mice brains.…”

“…Fluorescence imaging of perfused WT and 5xFAD mice revealed the effective permeation of the BBB by Cy5‐CP‐2‐LPs, leading to their accumulation in the brains of 5xFAD mice. Given the increased accumulation observed in the brains of 5xFAD mice, a condition that may be associated with a compromised BBB in the AD model, [ 73 ] and considering the limited inherent ability of naked liposomes to traverse the BBB, [ 74 ] the specific role of CP‐2 in facilitating BBB penetration was investigated. To discern the specific contribution of CP‐2 to BBB penetration, Cy5‐liposomes were conjugated to β‐alanine ethyl ester to generate Cy5‐β‐Ala‐LPs.…”

Huntingtin-associated protein 1 ameliorates neurological function rehabilitation by facilitating neurite elongation through TrKA-MAPK pathway in mice spinal cord injury

“…The function of Hap1 associated with the glucocorticoid signaling pathway is to participate in the hypothalamic response to abnormal stress-related disorders including degenerative diseases, such as HD and Parkinson’s, where abnormally high chronic cortisol levels were reported ( Karadima et al, 2012 ; Chen et al, 2023 ). Disruption of the regulatory homeostasis of glucocorticoid by Hap1 is considered a major risk factor for neurodegenerative diseases and neuropsychiatric disorders ( Chen et al, 2020 ).…”