Amino Acids

, Volume 38, Issue 2, pp 653–658 | Cite as

Critical role of transglutaminase and other stress proteins during neurodegenerative processes

  • Daniela Caccamo
  • Monica Currò
  • Salvatore Condello
  • Nadia Ferlazzo
  • Riccardo Ientile
Review Article

Abstract

Proteolytic stress, resulting from the intracellular accumulation of misfolded or aggregated proteins, which exceed the capacity of the ubiquitin–proteasome system to degrade them, plays a relevant role in neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s chorea. Most of toxic protein aggregates are characterised by the presence of isopeptide bonds (cross-links) catalysed by transglutaminase activity; further, several disease-specific proteins—tau, amyloid-beta, alpha-synuclein, huntingtin—are in vitro and/or in vivo substrates of transglutaminase 2. These findings suggest an important role for transglutaminase 2-mediated cross-linking reactions in neurodegeneration. Therefore, the use of transglutaminase activity inhibitors could ameliorate neuronal cell death. New therapeutic perspectives also arise from the possibility to prevent or reduce protein aggregation by enhancing the activation of heat shock proteins, which have been shown to be potent suppressors of neurodegeneration in cell cultures/animal models. Interestingly, some heat shock proteins have been shown to be in vitro or in vivo cross-linked by transglutaminase 2. These observations seem to suggest that transglutaminase activity could be involved in the stabilization of intracellular protein aggregates by interfering with proteasomal degradation of misfolded proteins. Further studies are needed to validate leading hypotheses and to open new prospects for developing therapeutic tools.

Keywords

Transglutaminases Tissue transglutaminase Heat shock proteins Protein aggregates Neurodegenerative diseases 

Abbreviations

AD

Alzheimer’s disease

PD

Parkinson’s disease

ALS

Amyotrophic lateral sclerosis

CSF

Cerebrospinal fluid

ECM

Extracellular matrix

GGEL

γ-Glutamyl-ε-lysine

HD

Huntington’s chorea

HSPs

Heat shock proteins

NF-kappa B

Nuclear factor-kappa B

NMDA

N-methyl-d-aspartate

RA

Retinoic acid

SCA

Spinocerebellar ataxia

SBMA

Spinobulbar muscular atrophy

TG(s)

Transglutaminase(s)

TG2

Tissue transglutaminase

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Daniela Caccamo
    • 1
  • Monica Currò
    • 1
  • Salvatore Condello
    • 1
  • Nadia Ferlazzo
    • 1
  • Riccardo Ientile
    • 1
  1. 1.Department of Biochemical, Physiological and Nutritional SciencesPoliclinico Universitario, University of MessinaMessinaItaly

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