Insulin-like growth factor 1 signaling in motor neuron and polyglutamine diseases: From molecular pathogenesis to therapeutic perspectives

Maria Pennuto; Udai Bhan Pandey; María José Polanco

doi:10.1016/j.yfrne.2020.100821

Insulin-like growth factor 1 signaling in motor neuron and polyglutamine diseases: From molecular pathogenesis to therapeutic perspectives

Front Neuroendocrinol. 2020 Apr:57:100821. doi: 10.1016/j.yfrne.2020.100821. Epub 2020 Jan 30.

Authors

Maria Pennuto¹, Udai Bhan Pandey², María José Polanco³

Affiliations

¹ Department of Biomedical Sciences (DBS), University of Padova, 35131 Padova, Italy; Veneto Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy; Padova Neuroscience Center (PNC), 35131 Padova, Italy; Myology Center (CIR-Myo), 35131 Padova, Italy. Electronic address: maria.pennuto@unipd.it.
² Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA; Division of Child Neurology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
³ Department of Pharmaceutic and Health Science, University San Pablo CEU, Campus Montepríncipe, 28925 Alcorcón, Madrid, Spain. Electronic address: maria.polancomora@ceu.es.

PMID: 32006533
DOI: 10.1016/j.yfrne.2020.100821

Abstract

The pleiotropic peptide insulin-like growth factor 1 (IGF-I) regulates human body homeostasis and cell growth. IGF-I activates two major signaling pathways, namely phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB/Akt) and Ras/extracellular signal-regulated kinase (ERK), which contribute to brain development, metabolism and function as well as to neuronal maintenance and survival. In this review, we discuss the general and tissue-specific effects of the IGF-I pathways. In addition, we present a comprehensive overview examining the role of IGF-I in neurodegenerative diseases, such as spinal and muscular atrophy, amyotrophic lateral sclerosis, and polyglutamine diseases. In each disease, we analyze the disturbances of the IGF-I pathway, the modification of the disease protein by IGF-I signaling, and the therapeutic strategies based on the use of IGF-I developed to date. Lastly, we highlight present and future considerations in the use of IGF-I for the treatment of these disorders.

Keywords: IGF-I signaling; Neurodegeneration; Post-translational modifications.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Amyotrophic Lateral Sclerosis / physiopathology
Animals
Glutamine / genetics
Humans
Insulin-Like Growth Factor I / genetics
Insulin-Like Growth Factor I / physiology*
MAP Kinase Signaling System / physiology
Motor Neurons / metabolism*
Muscular Atrophy, Spinal / physiopathology
Neurodegenerative Diseases / drug therapy
Neurodegenerative Diseases / physiopathology*
Peptides*
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / physiology*
ras Proteins / metabolism

Substances

Peptides
Glutamine
polyglutamine
Insulin-Like Growth Factor I
Proto-Oncogene Proteins c-akt
ras Proteins

Grants and funding

R21 NS111768/NS/NINDS NIH HHS/United States