New Peptide Drug for the Treatment of Alzheimer's Disease

Background

Alzheimer’s disease (AD) is estimated to affect about 50 million people worldwide and there are currently no effective treatments. The only approved drugs for AD, i.e. acetylcholinesterase inhibitors and NMDA receptor antagonists, have no effect on preserving neural connections and do not prolong patients’ lives. Cell biological studies related to neurodegenerative diseases have mainly targeted neuronal cell death and post-synaptic dysfunction.

Technology Overview

A team of OIST researchers however has elucidated the pre-synaptic mechanisms of Alzheimer’s disease and found that hyperphosphorylated tau (hTau) causes dynamin deficiency through the assembly of microtubules (MTs) to which the dynamin binds; impairing synaptic vesicle endocytosis and, consequently, signal transmission.

To prevent the toxic effects of hTau and recover signal transmission, the team developed a synthetic peptide, PHDP5, which inhibits MT-dynamin interaction and prevents tau protein-induced impairments of endocytosis. This is a promising new therapeutic approach that has shown to prevent the loss of synaptic function in AD-model mice, which after intranasal delivery are able to retain their cognitive functions comparable to wildtype mice.

.

Further Detail

Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model

The microtubule-dynamin binding inhibitor peptide PHDP5 rescues spatial learning and memory deficits in Alzheimer’s disease model mice

Benefits

• Restores synaptic function
• Middle molecule

Applications

• Drug development
• Neurodegenerative diseases
• Alzheimer’s disease