{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:14:01Z","timestamp":1791994441510,"version":"4.4.0"},"reference-count":23,"publisher":"Society for Neuroscience","issue":"18","license":[{"start":{"date-parts":[[2009,11,6]],"date-time":"2009-11-06T00:00:00Z","timestamp":1257465600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2009,5,6]]},"abstract":"<jats:p>The progressive myoclonus epilepsies, featuring the triad of myoclonus, seizures, and ataxia, comprise a large group of inherited neurodegenerative diseases that remain poorly understood and refractory to treatment. The<jats:italic>Cystatin B<\/jats:italic>gene is mutated in one of the most common forms of progressive myoclonus epilepsy, Unverricht\u2013Lundborg disease (EPM1).<jats:italic>Cystatin B<\/jats:italic>knockout in a mouse model of EPM1 triggers progressive degeneration of cerebellar granule neurons. Here, we report impaired redox homeostasis as a key mechanism by which Cystatin B deficiency triggers neurodegeneration. Oxidative stress induces the expression of Cystatin B in cerebellar granule neurons, and EPM1 patient-linked mutation of the<jats:italic>Cystatin B<\/jats:italic>gene promoter impairs oxidative stress induction of<jats:italic>Cystatin B<\/jats:italic>transcription. Importantly,<jats:italic>Cystatin B<\/jats:italic>knockout or knockdown sensitizes cerebellar granule neurons to oxidative stress-induced cell death. The Cystatin B deficiency-induced predisposition to oxidative stress in neurons is mediated by the lysosomal protease Cathepsin B. We uncover evidence of oxidative damage, reflected by depletion of antioxidants and increased lipid peroxidation, in the cerebellum of<jats:italic>Cystatin B<\/jats:italic>knock-out mice<jats:italic>in vivo<\/jats:italic>. Collectively, our findings define a pathophysiological mechanism in EPM1, whereby Cystatin B deficiency couples oxidative stress to neuronal death and degeneration, and may thus provide the basis for novel treatment approaches for the progressive myoclonus epilepsies.<\/jats:p>","DOI":"10.1523\/jneurosci.0682-09.2009","type":"journal-article","created":{"date-parts":[[2009,5,6]],"date-time":"2009-05-06T17:33:18Z","timestamp":1241631198000},"page":"5910-5915","source":"Crossref","is-referenced-by-count":121,"title":["Cystatin B Deficiency Sensitizes Neurons to Oxidative Stress in Progressive Myoclonus Epilepsy, EPM1"],"prefix":"10.1523","volume":"29","author":[{"given":"Maria 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