L-Rha and L-Rha Derivatives and Their Effects on Neurodegenerative Alzheimer's Disease

Project Summary
A rare sugar, L-rhamnose (L-Rha) and L-Rha-containing molecules demonstrated unique effects on
Alzheimer’s disease (AD). Despite its importance in human health, it is still not clear how L-Rha plays a
role in activation of the signaling pathways that modulate neurons in neurogenesis and the genetic factors
related to amyloid β and tau protein. Most studies on L-Rha have used L-Rha-rich oligosaccharides and
polysaccharides that are extracted from plants and bacteria, which make it challenging to identify the effect
of L-Rha itself and its derivatives on human health. A research team at the University of Toledo will design
and synthesize L-Rha-containing molecules with specific sizes and structures using an innovative and novel
microwave-assisted chemistry and investigate their effects on growth and transcriptional factors in neurons
that are related to the neurogenesis and development of AD. We hypothesize that specific conjugates
(glucose and glucuronic acid) and size (dimer and trimer, and oligomers) of L-Rha have optimum effects
on AD. Activation of Nrf2, a master regulator of antioxidant response to reactive oxygen species, by L-Rha
will be investigated in detail including effects on the reduction of PKB and GSK for controlling p-tau and
amyloid-β involved in Alzheimer disease. The synthesis methods will facilitate the production and
separation of L-Rha -containing compounds with high yields and purity. These molecules will help us gain
a better understanding of the effects of L-Rha sugar on AD treatment and new drug development.

Grant Number: 1R21AG095752-01
NIH Institute/Center: NIH
Principal Investigator: Peter Andreana