학술논문
Synapsin-caveolin-1 gene therapy preserves neuronal and synaptic morphology and prevents neurodegeneration in a mouse model of AD.
Document Type
article
Author
Wang, Shanshan; Leem, Joseph S; Podvin, Sonia; Hook, Vivian; Kleschevnikov, Natalia; Savchenko, Paul; Dhanani, Mehul; Zhou, Kimberly; Kelly, Isabella C; Zhang, Tong; Miyanohara, Atsushi; Nguyen, Phuong; Kleschevnikov, Alexander; Wagner, Steve L; Trojanowski, John Q; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P
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Subject
Language
Abstract
Alzheimer's disease (AD) is the most common form of neurodegeneration and cognitive dysfunction in the elderly. Identifying molecular signals that mitigate and reverse neurodegeneration in AD may be exploited therapeutically. Transgenic AD mice (PSAPP) exhibit learning and memory deficits at 9 and 11 months, respectively, with associated decreased expression of caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein necessary for synaptic and neuroplasticity. Neuronal-targeted gene therapy using synapsin-Cav-1 cDNA (SynCav1) was delivered to the hippocampus of PSAPP mice at 3 months using adeno-associated virus serotype 9 (AAV9). Bilateral SynCav1 gene therapy was able to preserve MLRs profile, learning and memory, hippocampal dendritic arbor, synaptic ultrastructure, and axonal myelin content in 9- and 11-month PSAPP mice, independent of reducing toxic amyloid deposits and astrogliosis. Our data indicate that SynCav1 gene therapy may be an option for AD and potentially in other forms of neurodegeneration of unknown etiology.