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Review
. 2021 Sep 17:13:723871.
doi: 10.3389/fnagi.2021.723871. eCollection 2021.

Motor Neuron Diseases and Neuroprotective Peptides: A Closer Look to Neurons

Emanuela Zuccaro  1   2   3 , Diana Piol  1 , Manuela Basso  4 , Maria Pennuto  1   2   3
Affiliations
Review

Motor Neuron Diseases and Neuroprotective Peptides: A Closer Look to Neurons

Emanuela Zuccaro et al. Front Aging Neurosci. .

Abstract

Motor neurons (MNs) are specialized neurons responsible for muscle contraction that specifically degenerate in motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS), spinal and bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Distinct classes of MNs degenerate at different rates in disease, with a particular class named fast-fatigable MNs (FF-MNs) degenerating first. The etiology behind the selective vulnerability of FF-MNs is still largely under investigation. Among the different strategies to target MNs, the administration of protective neuropeptides is one of the potential therapeutic interventions. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with beneficial effects in many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and more recently SBMA. Another neuropeptide that has a neurotrophic effect on MNs is insulin-like growth factor 1 (IGF-1), also known as somatomedin C. These two peptides are implicated in the activation of neuroprotective pathways exploitable in the amelioration of pathological outcomes related to MNDs.

Keywords: ALS (Amyotrophic lateral sclerosis); IGF-1 (insulin-like growth factor 1); PACAP (pituitary adenylate cyclase-activating polypeptide); motor neuron (MN); motor neuron disease (MND); spinal muscular atrophy (SMA); spinobulbar muscular atrophy (SBMA).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic of the motor system. Upper motor neurons (UMNs) project to lower motor neurons (LMNs) in the brainstem and spinal cord. LMNs innervate skeletal muscle fibers. Different classes of α-MNs innervate diverse skeletal muscle fibers. FF-MNs, fast-fatigable MNs. SFR-MNs, slow fatigue resistant MNs. FFR-MNs, fast fatigue resistant MNs.
FIGURE 2
FIGURE 2
Overview of the cellular and molecular alterations in MNDs. Several cellular and molecular alterations are common to distinct MNDs, including protein misfolding and aggregates, proteostasis impairment, oxidative stress, and mitochondrial dysfunction. IGF-1 and PACAP main signal transduction pathways are presented in the figure.
See this image and copyright information in PMC

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