GDNF synthesis, signaling, and retrograde transport in motor neurons.

Abstract:

:Glial cell line-derived neurotrophic factor (GDNF) is a 134 amino acid protein belonging in the GDNF family ligands (GFLs). GDNF was originally isolated from rat glial cell lines and identified as a neurotrophic factor with the ability to promote dopamine uptake within midbrain dopaminergic neurons. Since its discovery, the potential neuroprotective effects of GDNF have been researched extensively, and the effect of GDNF on motor neurons will be discussed herein. Similar to other members of the TGF-β superfamily, GDNF is first synthesized as a precursor protein (pro-GDNF). After a series of protein cleavage and processing, the 211 amino acid pro-GDNF is finally converted into the active and mature form of GDNF. GDNF has the ability to trigger receptor tyrosine kinase RET phosphorylation, whose downstream effects have been found to promote neuronal health and survival. The binding of GDNF to its receptors triggers several intracellular signaling pathways which play roles in promoting the development, survival, and maintenance of neuron-neuron and neuron-target tissue interactions. The synthesis and regulation of GDNF have been shown to be altered in many diseases, aging, exercise, and addiction. The neuroprotective effects of GDNF may be used to develop treatments and therapies to ameliorate neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). In this review, we provide a detailed discussion of the general roles of GDNF and its production, delivery, secretion, and neuroprotective effects on motor neurons within the mammalian neuromuscular system.

journal_name

Cell Tissue Res

journal_title

Cell and tissue research

authors

Cintrón-Colón AF,Almeida-Alves G,Boynton AM,Spitsbergen JM

doi

10.1007/s00441-020-03287-6

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

47-56

issue

1

eissn

0302-766X

issn

1432-0878

pii

10.1007/s00441-020-03287-6

journal_volume

382

pub_type

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