| First Author | Morrone CD | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 10 | Pages | e0165393 |
| PubMed ID | 27768761 | Mgi Jnum | J:255276 |
| Mgi Id | MGI:6100310 | Doi | 10.1371/journal.pone.0165393 |
| Citation | Morrone CD, et al. (2016) Effects of Neurotrophic Support and Amyloid-Targeted Combined Therapy on Adult Hippocampal Neurogenesis in a Transgenic Model of Alzheimer's Disease. PLoS One 11(10):e0165393 |
| abstractText | Although it is recognized that multi-drug therapies may be necessary to combat AD, there is a paucity of preclinical proof of concept studies. We present a combination treatment paradigm, which temporally affects different aspects of Alzheimer's disease (AD)-like pathology, specifically Abeta-toxicity and neurogenesis. At early stages of AD-like pathology, in TgCRND8 mice, we found that combating Abeta pathology with scyllo-inositol ameliorated deficits in neurogenesis. Older TgCRND8 mice with established amyloid load had decreased progenitor cell proliferation and survival compared to non-transgenic mice, regardless of scyllo-inositol treatment. The prolonged exposure to Abeta-pathology leads to deficits in the neurogenic niche, thus targeting Abeta alone is insufficient to rescue neurogenesis. To support the neurogenic niche, we combined scyllo-inositol treatment with leteprinim potassium (neotrofin), the latter of which stimulates neurotrophin expression. We show that the combination treatment of scyllo-inositol and neotrofin enhances neuronal survival and differentiation. We propose this proof of concept combination therapy of targeting Abeta-pathology and neurotrophin deficits as a potential treatment for AD. |
