ArticleHuman molecular genetics2012
The homocysteine-inducible endoplasmic reticulum (ER) stress protein Herp counteracts mutant α-synuclein-induced ER stress via the homeostatic regulation of ER-resident calcium release channel proteins.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
- HERPUD1 suppresses porcine epidemic diarrhea virus replication by recruiting HRD1 to degrade viral ORF3 protein.Journal of virology · 2026Article
- MAM-Mediated Mitochondrial CaBrain sciences · 2025Article
- HERPUD1, a Member of the Endoplasmic Reticulum Protein Quality Control Mechanism, may be a Good Target for Suppressing Tumorigenesis in Breast Cancer Cells.Turkish journal of pharmaceutical sciences · 2023Article
- Association of HERPUD1 genetic variant rs2217332 with age-related macular degeneration and polypoidal choroidal vasculopathy in an Indian cohort.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023Article
- SARS-CoV-2PeerJ · 2023Article
- Pathogenesis of α-Synuclein in Parkinson's Disease: From a Neuron-Glia Crosstalk Perspective.International journal of molecular sciences · 2022Review
- Herpud1 suppress angiotensin II induced hypertrophy in cardiomyocytes.Biochemistry and biophysics reports · 2022Article
- Brain regions susceptible to alpha-synuclein spreading.Molecular psychiatry · 2022Review
- Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome.International journal of molecular sciences · 2021Article
- Zinc transporter ZIP7 is a novel determinant of ferroptosis.Cell death & disease · 2021Article
- The Roles of the Ubiquitin-Proteasome System in the Endoplasmic Reticulum Stress Pathway.International journal of molecular sciences · 2021Review
- Circ_002117 binds to microRNA-370 and promotes endoplasmic reticulum stress-induced apoptosis in gastric cancer.Cancer cell international · 2020Article
- Human myeloperoxidase (hMPO) is expressed in neurons in the substantia nigra in Parkinson's disease and in the hMPO-α-synuclein-A53T mouse model, correlating with increased nitration and aggregation of α-synuclein and exacerbation of motor impairment.Free radical biology & medicine · 2019Article
- CDNF Protein Therapy in Parkinson's Disease.Cell transplantation · 2019Article
- Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles.Frontiers in neuroscience · 2019Review
- Linking the Endoplasmic Reticulum to Parkinson's Disease and Alpha-Synucleinopathy.Frontiers in neuroscience · 2019Review
- Herp Promotes Degradation of Mutant Huntingtin: Involvement of the Proteasome and Molecular Chaperones.Molecular neurobiology · 2018Article
- Article
- Parkinson's disease: experimental models and reality.Acta neuropathologica · 2018Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases. The mechanisms that lead to ER stress and whereby ER stress contributes to the degenerative cascades remain unclear but their understanding is critical to devising effective therapies. Here we show that knockdown of Herp (Homocysteine-inducible ER stress protein), an ER stress-inducible protein with an ubiquitin-like (UBL) domain, aggravates ER stress-mediated cell death induced by mutant α-synuclein (αSyn) that causes an inherited form of Parkinson's disease (PD). Functionally, Herp plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca(2+) release channels. Deletion of the UBL domain or pharmacological inhibition of proteasomes abolishes the Herp-mediated stabilization of ER Ca(2+) homeostasis. Furthermore, knockdown or pharmacological inhibition of ER Ca(2+) release channels ameliorates ER stress, suggesting that impaired homeostatic regulation of Ca(2+) channels promotes a protracted ER stress with the consequent activation of ER stress-associated apoptotic pathways. Interestingly, sustained upregulation of ER stress markers and aberrant accumulation of ER Ca(2+) release channels were detected in transgenic mutant A53T-αSyn mice. Collectively, these data establish a causative link between impaired ER Ca(2+) homeostasis and chronic ER stress in the degenerative cascades induced by mutant αSyn and suggest that Herp is essential for the resolution of ER stress through maintenance of ER Ca(2+) homeostasis. Our findings suggest a therapeutic potential in PD for agents that increase Herp levels or its ER Ca(2+)-stabilizing action.
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