Mechanisms of neurodegeneration and the synaptic basis of memory

In 2019, research on Alzheimer's disease focused on the further characterization of the mechanism of action and efficacy of the mutated form of the human Nerve Growth Factor hNGFp), NGF painless (hNGFp). In order for there to be a decrease in the number of beta amyloid plaques, a synergistic action of hNGFp and chemokine CCL9 which in turn is induced by this neurotrophin, is necessary. We compared the efficacy of hNGFp to that of wild type hNGF. We demonstrated that hNGFp has superior efficacy as the wild type hNGF does not cause a decrease in amyloid beta.
HNGFp was engineered based on a mutation of NGF present in a rare disease, Autonomic and Sensory Neuropathy type V (HSAN V). This year we continued to analyze the knockin mouse for this mutation, completing the tests that allowed us to confirm its validity as a mouse model of the disease.
In the field of neurotrophins, the conformation of the p75NTR receptor, which determines apoptosis and growth block of neurites, and the structure of the p75NTR ligand, proNGF, were also studied.
Furthermore, it was observed that neurogenesis in a mouse model of Alzheimer's disease is negatively influenced by the presence of beta amyloid oligomers, that is of the most toxic form of this protein.
A further publication concerns the early consequences of the expression of a mutated form of alpha synuclein, a protein involved in Parkinson's disease. It was observed that the expression of this protein determines early symptoms at the gastrointestinal level that precede the onset of motor disorders.