Sigma for synapses
How Cognition plans to protect synapse function in AD via sigma-2
By focusing on synapse protection instead of aggregate formation, Cognition Therapeutics Inc. has identified a new target for Alzheimer’s disease that it believes can block β amyloid’s toxic effects more efficiently than the standard approaches. The idea is that targeting the relatively understudied σ-2 receptor could preserve -- and maybe regenerate -- synapses, halting or reversing cognitive decline.
While recent research in neuropsychiatric disorders has sought new targets related to synaptic connectivity and function, research in neurodegenerative disorders has largely focused on protein aggregation, and AD in particular has fixated on attacking β amyloid clusters or tau-filled neurofibrillary tangles.
In AD, monomers of the β amyloid peptide join together in the brain to form large extracellular clumps that are hallmarks of the disease, but smaller oligomeric forms of the peptide that remain soluble are thought to do the majority of the damage to neurons and synapses.
Cognition believes β amyloid oligomers drive synapse loss -- and ultimately memory failure -- by binding to neurons and inducing abnormal intracellular signaling. While there’s no consensus on the identity of the neuronal receptor for β amyloid oligomers, Cognition has data suggesting it belongs to a protein complex that interacts with the σ-2 receptor, a synaptic