Could the Neuropeptide Substance P Protect Motor Neurons in ALS? | Research

The takeaway

Substance P levels are altered in the brain, spinal cord, and cerebrospinal fluid of ALS patients and animal models, with evidence suggesting it may contribute to selective motor neuron resistance.

Selective sparing
substance P may explain why certain motor neurons resist ALS degeneration

What the researchers found

Substance P is altered in ALS patients and may play a neuroprotective role by inhibiting excitotoxicity-induced motor neuron death, potentially contributing to the selective sparing of certain motor neuron populations.

Why it matters

ALS has no cure and limited treatment options. Understanding why certain motor neurons resist degeneration could reveal new therapeutic targets, and substance P's potential neuroprotective role opens a novel avenue for drug development.

The numbers in context

Worldwide obesity prevalence is increasing dramatically with significant economic burden.

How the study worked

Narrative review synthesizing clinical data on SP levels in ALS patients, preclinical studies of SP's neuroprotective effects, and mechanistic studies of SP's role in motor neuron excitability and survival.

Who was studied

Adults with obesity and cardiovascular/cerebrovascular risk

What this study cannot tell us

Review article synthesizing observational and preclinical data; causal relationship between SP levels and motor neuron protection not definitively established; SP has multiple functions throughout the nervous system complicating therapeutic targeting; no clinical trials of SP-based ALS therapies reported.

How to read the evidence

Preliminary evidence from clinical observations and preclinical studies. The neuroprotective hypothesis is plausible but unproven in clinical settings.

When this study was published

Published in 2024, synthesizing current understanding of substance P in ALS pathophysiology.

The bigger picture

The selective vulnerability of motor neurons in ALS is one of the disease's most puzzling features. If substance P contributes to protecting certain motor neuron populations, boosting SP signaling could potentially extend this protection to vulnerable neurons.

Questions still open

Could NK1R agonists slow motor neuron degeneration in ALS patients?
Is substance P deficiency a cause or consequence of motor neuron loss?
Can SP-based protection be enhanced in the most vulnerable motor neuron populations?

Common questions

What does substance P have to do with ALS?

Substance P is a neuropeptide that appears to be abnormally reduced in ALS patients' nervous systems. Research suggests it normally helps protect motor neurons from the toxic processes that kill them in ALS, and may explain why some motor neurons (like those controlling eye movement) are spared.

Could substance P become a treatment for ALS?

It's an early-stage idea, but the evidence that SP protects against excitotoxicity — a major motor neuron killer in ALS — makes it a promising therapeutic target worth investigating in future clinical trials.

Read the original research

Role of glucagon-like peptide-1 receptor agonists in the treatment of obesity, cardiovascular disease, and cerebrovascular disease.

Polish archives of internal medicine, 134(2)

View on PubMed ↗Publisher’s paper ↗

Citation

Tirandi, Amedeo; Montecucco, Fabrizio; Carbone, Federico; Liberale, Luca. (2024). Role of glucagon-like peptide-1 receptor agonists in the treatment of obesity, cardiovascular disease, and cerebrovascular disease.. Polish archives of internal medicine, 134(2). https://doi.org/10.20452/pamw.16658