Description:
Using our screening strategy we identified a new class of small molecules that binds simultaneously to monomeric and to membrane-bound alpha-synuclein. Moreover these molecules have a high affinity to Lipocalin 2 (Lcn2/NGAL). Lcn2 is a potent neurotoxic factor secreted by reactive astrocytes.
Pilot data for our compound in a chronic progressive model of Parkinson’s disease, showed that the hit compound is effective in promoting cortical neuron growth in a chronic mouse model, presumably via affecting the distribution between quiescent (healthy) and reactive (toxic) astrocytes. This unique double-pronged approach to Parkinson’s disease exploiting Lcn2 and alpha-synuclein binding properties in a single molecule can potentially deliver a very powerful therapeutic effect, as evidenced by in vitro and mouse data.
Figure 1. Transgenic PD mice treated with the hit compound of the invention.
(A) The compound increases the number of neurons in the cortex of
transgenic animal model for Parkinson‘s disease.
(B) The compound increases the astrocyte number in the same mice
(bottom right-hand panel).