| First Author | Fleming SM | Year | 2011 |
| Journal | Mol Cell Neurosci | Volume | 46 |
| Issue | 3 | Pages | 597-606 |
| PubMed ID | 21193046 | Mgi Jnum | J:171294 |
| Mgi Id | MGI:4949571 | Doi | 10.1016/j.mcn.2010.12.011 |
| Citation | Fleming SM, et al. (2011) A pilot trial of the microtubule-interacting peptide (NAP) in mice overexpressing alpha-synuclein shows improvement in motor function and reduction of alpha-synuclein inclusions. Mol Cell Neurosci 46(3):597-606 |
| abstractText | Abnormal accumulation of alpha-synuclein is associated with several neurodegenerative disorders (synucleinopathies), including sporadic Parkinson's disease (PD). Genetic mutations and multiplication of alpha-synuclein cause familial forms of PD and polymorphisms in the alpha-synuclein gene are associated with PD risk. Overexpression of alpha-synuclein can impair essential functions within the cell such as microtubule-dependent transport, suggesting that compounds that act on the microtubule system may have therapeutic benefit for synucleinopathies. In this study, mice overexpressing human wildtype alpha-synuclein under the Thy1 promoter (Thy1-aSyn) and littermate wildtype control mice were administered daily the microtubule-interacting peptide NAPVSIPQ (NAP; also known as davunetide or AL-108) intranasally for 2 months starting at 1 month of age, in a regimen known to produce effective concentrations of the peptide in mouse brain. Motor performance, coordination, and activity were assessed at the end of treatment. Olfactory function, which is altered in PD, was measured 1 month later. Mice were sacrificed at 4.5 months of age, and their brains examined for proteinase K-resistant alpha-synuclein inclusions in the substantia nigra and olfactory bulb. NAP-treated Thy1-aSyn mice showed a 38% decrease in the number of errors per step in the challenging beam traversal test and a reduction in proteinase K-resistant alpha-synuclein inclusions in the substantia nigra compared to vehicle treated transgenics. The data indicate a significant behavioral benefit and a long lasting improvement of alpha-synuclein pathology following administration of a short term (2 months) NAP administration in a mouse model of synucleinopathy. |
