Lingo-1: a novel target in therapy for Alzheimer's disease?

AD is a progressive, neurodegenerative disease characterized clinically by gradual cognitive decline including loss of memory, orientation and reasoning, and is pathologically characterized by accumulation of neurofibrillary tangles and amyloid plaques in the brain. These amyloid plaques have different rates of growth throughout neocortical and hippocampal regions, and are formed from oligomers of amyloid-β (Aβ) in the intracellular and extracellular space. Aβ is the result of proteolysis of amyloid precursor protein (APP) by β and γ-secretase enzymes. The accumulation of Aβ oligomers becomes progressively toxic and triggers the start of neurodegenerative processes (Hardy and Selkoe, 2002). Here we discuss the role of Lingo-1, or LERN1 (leucine-rich repeat neuronal protein 1) in this process, a transmembrane protein which is highly abundant in the brain and is implicated in numerous neurodegenerative disorders (Andrews and Fernandez-Enright, 2015), and demonstrate reasons suggesting its potential for a role in future AD therapy.