Critical role of transglutaminase and other stress proteins during neurodegenerative processes

  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},
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… 
Monitoring of transglutaminase2 under different oxidative stress conditions
TG2 role in cell response to redox state imbalance both under physiological and pathological conditions, such as neurodegenerative disorders, inflammation, autoimmune diseases and cataractogenesis, in which oxidative stress plays a pathogenetic role and also accelerates disease progression is reviewed.
Transglutaminase is a Therapeutic Target for Oxidative Stress, Excitotoxicity and Stroke: A new Epigenetic Kid on the Cns Block
  • M. Basso, R. Ratan
  • Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2013
An evolving model in which TG2 is a critical mediator between pathologic signaling and epigenetic modifications that lead to gene repression is outlined, which may derive from their ability to restore homeostasis by removing inappropriate deactivation of adaptive genetic programs by oxidative stress or extrasynaptic glutamate receptor signaling.
Transglutaminase Inhibition Protects against Oxidative Stress-Induced Neuronal Death Downstream of Pathological ERK Activation
These studies suggest that multiple TG isoforms, not only TG2, participate in oxidative stress-induced cell death signaling; and that isoform nonselective inhibitors of TG will be most efficacious in combating oxidative death in neurological disorders.
Transglutaminase 2 silencing reduced the beta-amyloid-effects on the activation of human THP-1 cells
Results indicate that TG2 up-regulation is required for the functional THP-1 monocyte activation induced by Aβ1–42, and suggests thatTG2 inhibition may represent a therapeutic target to ameliorate the inflammation and progression in Alzheimer’s disease.
Cellular functions of tissue transglutaminase.
Transglutaminase 6 Is Colocalized and Interacts with Mutant Huntingtin in Huntington Disease Rodent Animal Models
The results demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis and the contribution of its enzymatic activity for the total aggregate load in SH-SY5Y cells, and point towards a role of TG6 in disease pathogenesis via mHTT aggregate formation.
Modulation of transglutaminase 2 activity in H9c2 cells by protein kinase A and protein kinase C signalling
Data have shown TG2 activity to be stimulated via PKA and PKC-dependent signalling pathways in H9c2 cells and suggest a role for TG2 in cytoprotection-induced via these two protein kinases.


Transglutaminase Is Linked to Neurodegenerative Diseases
  • N. Muma
  • Biology, Chemistry
    Journal of neuropathology and experimental neurology
  • 2007
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.
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
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
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
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
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
Functional aspects of the different types of chaperones suggest their uses as potential therapeutic agents against different type of degenerative diseases, including neurodegenerative disorders.