Critical role of transglutaminase and other stress proteins during neurodegenerative processes

@article{Caccamo2009CriticalRO,
  title={Critical role of transglutaminase and other stress proteins during neurodegenerative processes},
  author={Daniela Caccamo and Monica Curr{\`o} and Salvatore Condello and Nadia Ferlazzo and Riccardo Ientile},
  journal={Amino Acids},
  year={2009},
  volume={38},
  pages={653-658}
}
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… 
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References

SHOWING 1-10 OF 53 REFERENCES
Transglutaminase Is Linked to Neurodegenerative Diseases
  • N. Muma
  • Biology, Chemistry
    Journal of neuropathology and experimental neurology
  • 2007
TLDR
In conclusion, inhibition of transglutaminase either via drug treatments or molecular approaches is beneficial for the treatment of HD transgenic mice but has yet to be explored for the other neurodegenerative diseases.
Transglutaminases: nature's biological glues.
TLDR
The structural and regulatory features important in mammalian Tgases are detail, with particular focus on the ubiquitous type 2 tissue enzyme, and some of the present and future biotechnological applications are included.
Differential Expression of Multiple Transglutaminases in Human Brain
TLDR
It is demonstrated by reverse transcriptase-polymerase chain reaction and immunological methods with specific antibodies that in fact three members of the transglutaminase family of enzymes are involved in normal neuronal structure and function, but their elevated expression and cross-linking activity may also contribute to neuronal degenerative disease.
Tissue transglutaminase and the stress response
TLDR
The underlying mechanisms of TG2 up-regulation induced by various stimuli including glutamate exposure, calcium influx, oxidative stress, UV, and inflammatory cytokines are discussed, agreeing with a postulated role for transglutaminases in molecular mechanisms involved in several diseases.
Transglutaminase 2 ablation leads to defective function of mitochondrial respiratory complex I affecting neuronal vulnerability in experimental models of extrapyramidal disorders
TLDR
It is shown that ablation of TG2 in knockout mice causes a reduced activity of mitochondrial complex I associated with an increased activity of complex II in the whole forebrain and striatum, suggesting that TG2 is involved in the regulation of the respiratory chain both in physiology and pathology.
Transglutaminase 2 inhibitors and their therapeutic role in disease states.
Transglutaminase facilitates the formation of polymers of the β-amyloid peptide
Tissue transglutaminase-induced aggregation of α-synuclein: Implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies
TLDR
Findings suggest that tTGase activity leads to α-synuclein aggregation to form Lewy bodies and perhaps contributes to neurodegeneration.
Protein‐misfolding diseases and chaperone‐based therapeutic approaches
TLDR
Functional aspects of the different types of chaperones suggest their uses as potential therapeutic agents against different type of degenerative diseases, including neurodegenerative disorders.
...
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