Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.

Publication date: Feb 15, 2024

HACE1 is a member of the HECT domain-containing E3 ligases with 909 amino acid residues, containing N-terminal ankyrin-repeats (ANK) and C-terminal HECT domain. Previously, it was shown that HACE1 is inactive in human tumors and plays a crucial role in the initiation, progression, and invasion of malignant tumors. Recent studies indicated that HACE1 might be closely involved in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. HACE1 interacts with its substrates, including Ras-related C3 botulinum toxin substrate 1 (Rac1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumor necrosis factor receptor (TNFR), and optineurin (OPTN), through which participates in several pathophysiological processes, such as oxidative stress, autophagy and inflammation. Therefore, in this review, we elaborately describe the essential substrates of HACE1 and illuminate the pathophysiological processes by which HACE1 is involved in neurodegenerative diseases. We provide a new molecular target for neurodegenerative diseases.

Concepts Keywords
Biomed HACE1
Parkinson Neurodegenerative disease
Pharmacother Nrf2
Promising OPTN
Tumor Rac1

Semantics

Type Source Name
disease MESH pathogenesis
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH tumors
disease MESH Alzheimer’s disease
disease MESH Parkinson’s disease
disease MESH Huntington’s disease
drug DRUGBANK Rasagiline
disease MESH oxidative stress
pathway KEGG Autophagy
disease MESH inflammation

Original Article

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