The Double-Edged Effects of Substance P in the Pathology of Alzheimer’s Disease

Alzheimer's disease is an irreversible neurodegenerative disease that manifests clinically as memory loss and so on. Neuroinflammation plays an important role in Alzheimer's disease. Meanwhile, widely distributed throughout the central nervous system, substance P exhibits important pro-inflammatory properties. The level of substance P is found to correlate with the course of Alzheimer's disease. Substance P can modulate the protein hydrolysis of amyloid precursor protein, the voltage-gated potassium channel, and the protein hydrolysis of this channel, exerting neuroprotective effects. At the same time, substance P can also exert damaging effects by mediating neuroinflammation, inhibiting cellular autophagy, activating mast cells, acting on leukocytes and altering blood-brain barrier permeability. Based on the complex manifestations of substance P in Alzheimer's disease, this review discusses both protective and damaging mechanisms, and plausible explanations for the double-edged effect of substance P, providing an outlook for future research focusing on substance P and Alzheimer's disease.