Motor neuron diseases (MNDs) are a group of fatal, neurodegenerative disorders with different etiology, clinical course and presentation, caused by the loss of upper and lower motor neurons (MNs). MNs are highly specialized cells equipped with long, axonal processes; axonal defects are some of the main players underlying the pathogenesis of these disorders. Microtubules are key components of the neuronal cytoskeleton characterized by dynamic instability, switching between rapid polymerization and shrinkage. Proteins of the stathmin family affect microtubule dynamics regulating the assembly and the dismantling of tubulin. Stathmin-2 (STMN2) is one of the most abundantly expressed genes in MNs. Following axonal injury, STMN2 expression is upregulated, and the protein is transported toward the growth cones of regenerating axons. STMN2 has a critical role in axonal maintenance, and its dysregulation plays an important role in neurodegenerative processes. Stathmin-1 (STMN1) is a ubiquitous protein that is highly expressed during the development of the nervous system, and its phosphorylation controls microtubule dynamics. In the present review, we summarize what is currently known about the involvement of stathmin alterations in MNDs and the potential therapeutic effect of their modulation, with a specific focus on the most common forms of MND, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

Stathmins and Motor Neuron Diseases: Pathophysiology and Therapeutic Targets / D. Gagliardi, E. Pagliari, M. Meneri, V. Melzi, F. Rizzo, G.P. Comi, S.P. Corti, M.M. Taiana, M. Nizzardo. - In: BIOMEDICINES. - ISSN 2227-9059. - 10:3(2022 Mar), pp. 711.1-711.10. [10.3390/biomedicines10030711]

Stathmins and Motor Neuron Diseases: Pathophysiology and Therapeutic Targets

D. Gagliardi
Co-primo
Writing – Original Draft Preparation
;
E. Pagliari
Co-primo
Writing – Original Draft Preparation
;
M. Meneri
Secondo
Writing – Original Draft Preparation
;
F. Rizzo
Writing – Review & Editing
;
G.P. Comi
Writing – Review & Editing
;
S.P. Corti
Supervision
;
M.M. Taiana
Penultimo
Conceptualization
;
M. Nizzardo
Ultimo
Supervision
2022

Abstract

Motor neuron diseases (MNDs) are a group of fatal, neurodegenerative disorders with different etiology, clinical course and presentation, caused by the loss of upper and lower motor neurons (MNs). MNs are highly specialized cells equipped with long, axonal processes; axonal defects are some of the main players underlying the pathogenesis of these disorders. Microtubules are key components of the neuronal cytoskeleton characterized by dynamic instability, switching between rapid polymerization and shrinkage. Proteins of the stathmin family affect microtubule dynamics regulating the assembly and the dismantling of tubulin. Stathmin-2 (STMN2) is one of the most abundantly expressed genes in MNs. Following axonal injury, STMN2 expression is upregulated, and the protein is transported toward the growth cones of regenerating axons. STMN2 has a critical role in axonal maintenance, and its dysregulation plays an important role in neurodegenerative processes. Stathmin-1 (STMN1) is a ubiquitous protein that is highly expressed during the development of the nervous system, and its phosphorylation controls microtubule dynamics. In the present review, we summarize what is currently known about the involvement of stathmin alterations in MNDs and the potential therapeutic effect of their modulation, with a specific focus on the most common forms of MND, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).
ALS; SMA; STMN1; STMN2; axonal defects; cytoskeleton; microtubules; motor neuron diseases; stathmin;
Settore MED/26 - Neurologia
   Stathmin-2 in Spinal Muscular Atrophy (SMA): assessing molecular and therapeutic role in SMA human and murine models
   FONDAZIONE CARIPLO
   2020-3623
mar-2022
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/919502
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