Activation Of Tyrosine Phosphatases In The Progression Of Alzheimer'S Disease

Patients with Alzheimer's disease (AD) have progressive memory loss, inability to reason, and display anxiety that accelerates disease progression. Evidence points to two deficits: 1) the brain fails to respond to insulin that regulates the formation of neuron connec-tions required to store memories, and 2) deficits arise in the brain's endogenous cannabinoid signaling that regulates mood and pre-vents anxiety (Aso and Ferrer, 2014). In addition, leptin signaling, important in regulating hypothalamic synaptic plasticity and cogni-tive function is also affected in AD (McGregor and Harvey, 2018). Until now, no single treatment targeting these three signaling defi-cits has been proposed. The tyrosine phosphatase PTP1B (Ptpn1) blocks brain insulin and leptin signaling (Pandey et al., 2013) and prevents endogenous cannabinoid production (Qin et al., 2015b) and is elevated in the brain of AD mice (Ricke et al., 2020). Thus, PTP1B is a plausible target for AD.