{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:59:55Z","timestamp":1793674795967,"version":"4.5.1"},"reference-count":139,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Birla Institute of Technology and Science-Pilani","award":["OPERA"],"award-info":[{"award-number":["OPERA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Accumulation of misfolded proteins is a common phenomenon of several neurodegenerative diseases. The misfolding of proteins due to abnormal polyglutamine (PolyQ) expansions are linked to the development of PolyQ diseases including Huntington\u2019s disease (HD). Though the genetic basis of PolyQ repeats in HD remains prominent, the primary molecular basis mediated by PolyQ toxicity remains elusive. Accumulation of misfolded proteins in the ER or disruption of ER homeostasis causes ER stress and activates an evolutionarily conserved pathway called Unfolded protein response (UPR). Protein homeostasis disruption at organelle level involving UPR or ER stress response pathways are found to be linked to HD. Due to dynamic intricate connections between ER and mitochondria, proteins at ER-mitochondria contact sites (mitochondria associated ER membranes or MAMs) play a significant role in HD development. The current review aims at highlighting the most updated information about different UPR pathways and their involvement in HD disease progression. Moreover, the role of MAMs in HD progression has also been discussed. In the end, the review has focused on the therapeutic interventions responsible for ameliorating diseased states via modulating either ER stress response proteins or modulating the expression of ER-mitochondrial contact proteins.<\/jats:p>","DOI":"10.3390\/ijms23020780","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Impact of ER Stress and ER-Mitochondrial Crosstalk in Huntington\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-4744","authenticated-orcid":false,"given":"Shuvadeep","family":"Maity","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science (BITS)-Pilani (Hyderabad Campus), Shameerpet-Mandal, Hyderabad 500078, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8620-6197","authenticated-orcid":false,"given":"Pragya","family":"Komal","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science (BITS)-Pilani (Hyderabad Campus), Shameerpet-Mandal, Hyderabad 500078, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishali","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science (BITS)-Pilani (Hyderabad Campus), Shameerpet-Mandal, Hyderabad 500078, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshika","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science (BITS)-Pilani (Hyderabad Campus), Shameerpet-Mandal, Hyderabad 500078, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Tungekar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science (BITS)-Pilani (Hyderabad Campus), Shameerpet-Mandal, Hyderabad 500078, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaani","family":"Chandrasekar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science (BITS)-Pilani (Hyderabad Campus), Shameerpet-Mandal, Hyderabad 500078, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1126\/science.3155875","article-title":"Evidence for Degenerative and Regenerative Changes in Neostriatal Spiny Neurons in Huntington\u2019s Disease","volume":"227","author":"Graveland","year":"1985","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes","volume":"72","author":"MacDonald","year":"1993","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20075","DOI":"10.1073\/pnas.1320626110","article-title":"Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation","volume":"110","author":"Crick","year":"2013","journal-title":"Proc. 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