{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:16:17Z","timestamp":1790270177716,"version":"4.1.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2016,1,12]]},"abstract":"<jats:p>Aberrant neuronal network activity associated with neuronal hyperexcitability seems to be an important cause of cognitive decline in aging and Alzheimer\u2019s disease (AD). Out of many antiepileptics, only levetiracetam improved cognitive dysfunction in AD patients and AD animal models by reducing hyperexcitability. As impaired inhibitory interneuronal function, rather than overactive neurons, seems to be the underlying cause, improving impaired neuronal function rather than quieting overactive neurons might be relevant in explaining the lack of activity of the other antiepileptics. Interestingly, improvement of cognitive deficits by levetiracetam caused by small levels of soluble A\u03b2 was accompanied by improvement of synaptic function and plasticity. As the negative effects of A\u03b2 on synaptic plasticity strongly correlate with mitochondrial dysfunction, wehypothesized that the effect of levetiracetam on synaptic activity might be raised by an improved mitochondrial function. Accordingly, we investigated possible effects of levetiracetam on neuronal deficits associated with mitochondrial dysfunction linked to aging and AD. Levetiracetam improved several aspects of mitochondrial dysfunction including alterations of fission and fusion balance in a cell model for aging and early late-onset AD. We demonstrate for the first time, using immunohistochemistry and proteomics, that the synaptic vesicle protein 2A (SV2a), the molecular target of levetiracetam, is expressed in mitochondria. In addition, levetiracetam shows significant effect on the opening of the mitochondrial permeability transition pore. Importantly, the effects of levetiracetam were significantly abolished when SV2a was knockdown using siRNA. In conclusion, interfering with the SV2a protein at the mitochondrial level and thereby improving mitochondrial function might represent an additional therapeutic effect of levetiracetam to improve symptoms of late-onset AD.<\/jats:p>","DOI":"10.3233\/jad-150687","type":"journal-article","created":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T10:11:24Z","timestamp":1452247884000},"page":"201-215","source":"Crossref","is-referenced-by-count":62,"title":["A Mitochondrial Role of SV2a Protein in Aging and Alzheimer\u2019s Disease: Studies with Levetiracetam"],"prefix":"10.1177","volume":"50","author":[{"given":"Carola","family":"Stockburger","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Frankfurt\/M, Biocenter, Frankfurt\/M, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Miano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Frankfurt\/M, Biocenter, 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