{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T22:52:23Z","timestamp":1783205543167,"version":"3.54.6"},"reference-count":180,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01 NS085054"],"award-info":[{"award-number":["R01 NS085054"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>In degenerative neurological disorders such as Parkinson\u2019s disease, a convergence of widely varying insults results in a loss of dopaminergic neurons and, thus, the motor symptoms of the disease. Dopamine replacement therapy with agents such as levodopa is a mainstay of therapy. Cerebellar ataxias, a heterogeneous group of currently untreatable conditions, have not been identified to have a shared physiology that is a target of therapy. In this review, we propose that perturbations in cerebellar Purkinje neuron intrinsic membrane excitability, a result of ion channel dysregulation, is a common pathophysiologic mechanism that drives motor impairment and vulnerability to degeneration in cerebellar ataxias of widely differing genetic etiologies. We further propose that treatments aimed at restoring Purkinje neuron intrinsic membrane excitability have the potential to be a shared therapy in cerebellar ataxia akin to levodopa for Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/life13061350","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T03:59:56Z","timestamp":1686196796000},"page":"1350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6125-5996","authenticated-orcid":false,"given":"Haoran","family":"Huang","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2742-6469","authenticated-orcid":false,"given":"Vikram G.","family":"Shakkottai","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S1474-4422(10)70183-6","article-title":"Autosomal dominant cerebellar ataxias: Polyglutamine expansions and beyond","volume":"9","author":"Durr","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s12311-018-0985-7","article-title":"Purkinje Neurons: Development, Morphology, and Function","volume":"17","author":"Hirano","year":"2018","journal-title":"Cerebellum"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-012-1000-x","article-title":"Brain pathology of spinocerebellar ataxias","volume":"124","author":"Seidel","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s00234-021-02682-2","article-title":"Conventional MRI findings in hereditary degenerative ataxias: A pictorial review","volume":"63","author":"Cocozza","year":"2021","journal-title":"Neuroradiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11795","DOI":"10.1523\/JNEUROSCI.0905-11.2011","article-title":"Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1","volume":"31","author":"Hourez","year":"2011","journal-title":"J. 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