Title:Substance P and Alzheimer’s Disease: Emerging Novel Roles
Volume: 13
Issue: 9
Author(s): Cinzia Severini, Carla Petrella and Pietro Calissano
Affiliation:
Keywords:
Alzheimer’s disease, anti-amyloidogenic activity, neuroprotection, substance P, tachykinins, potassium channels.
Abstract: Alzheimer's disease (AD) is an irreversible neurodegenerative disease, clinically characterized by progressive
impairments of memory and cognition. The hallmarks of AD are neurofibrillary tangles, mainly constituted by altered
phosphorylated and truncated portions of tau protein, and the abnormal extracellular deposition of neurotoxic beta amyloid
(Aβ) peptides, derived from the proteolytic processing of amyloid precursor protein (APP). According to the amyloid
hypothesis, Aβ is considered to be linked to the selective neurodegeneration seen in AD. Recent evidence points to an increase
in voltage-gated potassium (Kv) channel currents in the etiology of Aβ-induced neuronal apoptosis.
Substance P (SP) is an 11-aa neuropeptide, member of the tachykinin family, broadly distributed in the Central Nervous
System where it acts as a neurotransmitter, neuromodulator, and neurotrophic factor. This peptide may play an important
role in neurodegenerative disorders, since reduced levels of SP were found in brain areas and spinal fluid of AD patients.
In addition to its neuroprotective properties, it was recently demonstrated that SP is able to stimulate non-amyloidogenic
APP processing, thereby reducing the possibility of generation of toxic Aβ peptides in the brain. Recent studies, using in
vitro and in vivo models, have also shown that the neuroprotective role of SP against Aβ could be related to its ability of
modulate Kv channel currents.
In this review, we briefly summarized the current findings on the neurotrophic and neuroprotective effects of SP, providing
information about its anti-amyloidogenic and anti-Aβ toxicity role.