Lenti‐GDNF Gene Therapy Protects Against Alzheimer's Disease‐Like Neuropathology in 3xTg‐AD Mice and MC65 Cells

Abstract

GDNF induced neuroprotection in the AD experimental models used. Lentiviral vectors engineered to overexpress GDNF showed to be safe and effective, both as a potential gene therapy and as a tool to uncover the mechanisms of GDNF neuroprotection, including cross talk between astrocytes and neurons in the injured brain.

Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice

“…Instead, the pathology is characterized by gradual increase in the number of amyloid plaques surrounded by chronic neuroinflammation [30] and abnormalities in synaptic microstructure [29]. We found no effect of CDNF treatment on amyloid pathology, which is in line with our earlier observations of no change in brain amyloid load after manipulation of functional TrkB-receptor levels [27] or partial BDNF gene knockout [28], as well as with a recent study reporting lack of effect on amyloid levels by GDNF gene therapy in APP/PS1/tau transgenic mice [9]. Neither could we verify any obvious anti-inflammatory effect of CDNF around the injection site.…”

The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease

“…Furthermore, it has reported that 10-month-old 3xTg-AD mice subjected to 6 months of overexpressing GDNF (recombinant lentiviral vectors), showed improvement in the learning and memory. This GDNF neuroprotective effect induced a potent upregulation of BDNF, indicating that together may important against neurons atrophy and degeneration [110].…”

Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9

“…One of such advances involves gene silencing, one of the main therapeutic approaches, through recruitment of the cellular RNA interference A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 10 (RNAi) pathway. However, some studies have recently reported cellular toxicity caused by short-hairpin RNAs (shRNAs) in mouse and rat brains [47,48].…”