The role of autophagy: What can be learned from the genetic forms of amyotrophic lateral sclerosis

Livia Pasquali, Riccardo Ruffoli, Federica Fulceri, Sara Pietracupa, Gabriele Siciliano, Antonio Paparelli, Francesco Fornai

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by loss of motor neurons both in the brain and spinal cord, which dramatically reduces life expectancy. ALS occurs either in familial ALS or, more frequently, in sporadic ALS forms. Several mechanisms have been postulated to underlie motor neuron death. In the present paper, starting from some of the genes related to familial ALS, we overview and discuss their potential role in modifying of the physiological clearance of altered proteins and organelles in motor neurons. Special emphasis is placed on the role of autophagy, which seems to prevail as a protein clearing system over other multienzymatic pathways such as the proteasome within motor neurons. The evidence which links an altered autophagy to the onset of motor neuron death proposes that this biochemical pathway might represent a final common mechanism underlying both inherited and sporadic forms of ALS. In light of these findings we also analyze the potential significance of a novel association between ALS, altered autophagy, and mutations of nuclear proteins such as TAR-DNA-Binding Protein 43 and fused in sarcoma/translated in liposarcoma. Such an association appears to be critical since it is now well demonstrated that all sporadic and most familiar forms of ALS are characterized by altered deposition and mislocalization of TAR-DNA-Binding Protein 43. These novel insights into the pathogenesis of ALS may lead to the identification of novel strategies to promote motor neuron survival.

Original languageEnglish
Pages (from-to)268-278
Number of pages11
JournalCNS and Neurological Disorders - Drug Targets
Volume9
Issue number3
Publication statusPublished - 2010

Fingerprint

Autophagy
Amyotrophic Lateral Sclerosis
Motor Neurons
DNA-Binding Proteins
Liposarcoma
Proteasome Endopeptidase Complex
Nuclear Proteins
Life Expectancy
Sarcoma
Neurodegenerative Diseases
Organelles
Spinal Cord
Proteins
Mutation
Amyotrophic lateral sclerosis 1
Brain
Genes

Keywords

  • Autophagosome
  • Frontotemporal dementia
  • Fused in sarcoma/translated in liposarcoma
  • Genetics of amytrophic lateral sclerosis
  • Motor neuron
  • Tar-dna-binding protein 43
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Pasquali, L., Ruffoli, R., Fulceri, F., Pietracupa, S., Siciliano, G., Paparelli, A., & Fornai, F. (2010). The role of autophagy: What can be learned from the genetic forms of amyotrophic lateral sclerosis. CNS and Neurological Disorders - Drug Targets, 9(3), 268-278.

The role of autophagy : What can be learned from the genetic forms of amyotrophic lateral sclerosis. / Pasquali, Livia; Ruffoli, Riccardo; Fulceri, Federica; Pietracupa, Sara; Siciliano, Gabriele; Paparelli, Antonio; Fornai, Francesco.

In: CNS and Neurological Disorders - Drug Targets, Vol. 9, No. 3, 2010, p. 268-278.

Research output: Contribution to journalArticle

Pasquali, L, Ruffoli, R, Fulceri, F, Pietracupa, S, Siciliano, G, Paparelli, A & Fornai, F 2010, 'The role of autophagy: What can be learned from the genetic forms of amyotrophic lateral sclerosis', CNS and Neurological Disorders - Drug Targets, vol. 9, no. 3, pp. 268-278.
Pasquali L, Ruffoli R, Fulceri F, Pietracupa S, Siciliano G, Paparelli A et al. The role of autophagy: What can be learned from the genetic forms of amyotrophic lateral sclerosis. CNS and Neurological Disorders - Drug Targets. 2010;9(3):268-278.
Pasquali, Livia ; Ruffoli, Riccardo ; Fulceri, Federica ; Pietracupa, Sara ; Siciliano, Gabriele ; Paparelli, Antonio ; Fornai, Francesco. / The role of autophagy : What can be learned from the genetic forms of amyotrophic lateral sclerosis. In: CNS and Neurological Disorders - Drug Targets. 2010 ; Vol. 9, No. 3. pp. 268-278.
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