認知症状や神経症状を示す神経変性疾患の治療薬開発

抄録

Patients with neurodegenerative diseases (NDDs) are rapidly increasing worldwide. Alzheimer’s disease (AD), frontotemporal lobar degeneration (FTLD), Huntington’s disease (HD), and other several diseases are classified as NDDs; however, no therapeutic drugs have been developed yet.

In NDDs, protein oligomers and aggregates are formed in neuronal and glial cells and they trigger neuronal cell death and axonal degeneration. We discovered several chemicals and proteins can reverse these phenomena. In this symposium, we show phorbol 12-myristate 13-acetate (PMA) and a certain saccharide significantly inhibits aggregate formation and promotes neurite regeneration in cell culture model of FTLD and AD.

We expressed R406W mutant tau protein found in FTLD patients in SH-SY5Y human neuronal cells as FTLD cell culture model. FTLD neuronal cells showed intracellular aggregate formation and impaired neurite growth. Addition of PMA showed 60% decrease of aggregates. PMA also recovered neurite growth to the normal level. We cultured SH-SY5Y cells in the medium containing b-amyloid (1-42) as AD cell culture model. In these cells, neurite growth was deceased to less than 50% of controls, but addition of PMA dramatically recovered neurite extension in AD culture model cells. The other, a certain saccharide showed the almost same effects as PMA. These results suggest PMA and a certain saccharide have unexpected potentials for the drug development against NDDs (we will talk what is ‘a certain saccharide’ in symposium but please forgive that we do not open the name in abstract).