HERPUD1 Protein is a protein encoded by the HERPUD1 gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
HERPUD1 (Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain protein 1) is a 390-amino acid protein containing multiple structural domains:
The protein forms homodimers and is localized to the ER membrane with a type II membrane topology[1].
In neurons, HERPUD1 plays a critical role in multiple cellular processes[2][3]:
HERPUD1 is constitutively expressed in neurons and is upregulated during ER stress conditions[5].
The HERPUD1 field has expanded significantly with key discoveries in protein structure[1:1], disease associations[7:1][12], and therapeutic potential[11:1].
T. Kokame, Y. Okada, T. Ohsawa, et al. HERPUD1 is localized to the endoplasmic reticulum and involved in ER stress response. Cell Structure and Function. 2002. ↩︎ ↩︎
S. H. Kim, J. H. Lim, J. H. Kim, et al. Homocysteine and ER stress: the role of HERPUD1 in cellular protection. Biochimie. 2015. ↩︎
J. Wang, H. Yin, Y. Li, et al. HERPUD1 mediates ER-associated degradation of misfolded proteins. Journal of Cell Science. 2006. ↩︎
Y. Meng, Y. Wang, S. Li, et al. HERPUD1 regulates calcium homeostasis in neurons under ER stress. Cell Calcium. 2018. ↩︎
K. Kaneko, T. T. Nakamura, K. Yoshida, et al. HERPUD1 is upregulated in the brains of patients with Alzheimer's disease. Neurobiology of Aging. 2014. ↩︎
Y. J. Hwang, J. H. Yang, H. S. Kim, et al. Association of HERPUD1 polymorphisms with Alzheimer's disease. Journal of Alzheimer's Disease. 2014. ↩︎
K. H. van de Laar, L. M. Havekes, J. C. van Swieten, et al. Genome-wide association study identifies HERPUD1 variants for Alzheimer's disease. Neurobiology of Aging. 2014. ↩︎ ↩︎
S. C. Cho, M. H. Park, E. B. Lee, et al. ER stress and HERPUD1 response in Parkinson's disease models. Parkinsonism & Related Disorders. 2016. ↩︎
H. Chen, J. Liu, L. Wang, et al. Protective role of HERPUD1 in TDP-43 proteinopathy models of ALS. Acta Neuropathologica Communications. 2019. ↩︎
L. Yin, L. Li, Y. Wang, et al. HERPUD1 deficiency exacerbates mitochondrial dysfunction in neurodegenerative models. Cell Reports. 2020. ↩︎
X. Li, M. Cheng, Y. Zhou, et al. Targeting ER stress pathways: therapeutic potential of HERPUD1 modulation. Pharmacological Research. 2021. ↩︎ ↩︎
M. Yoshida, T. Tomimoto, K. Tanaka, et al. ER stress and protein quality control in neurodegenerative diseases. Trends in Neurosciences. 2016. ↩︎