Catalytically active tissue transglutaminase colocalises with Aβ pathology in Alzheimer's disease mouse models.

Alzheimer's disease (AD) is characterised by amyloid-beta (Aβ) protein deposition in the brain. Posttranslational modifications in Aβ play an important role in Aβ deposition. Tissue transglutaminase (tTG) is an enzyme involved in posttranslational cross-linking of proteins.

Tissue transglutaminase-catalysed cross-linking induces Apolipoprotein E multimers inhibiting Apolipoprotein E's protective effects towards amyloid-beta-induced toxicity.

Cerebral amyloid angiopathy (CAA) is a pathological hallmark of Alzheimer's disease (AD) and characterized by deposition of amyloid-β (Aβ) protein and smooth muscle cell (SMC) death in cerebral vessel walls. Apolipoprotein E (ApoE) is of importance in both Aβ accumulation and Aβ-mediated toxicity towards SMCs in the cerebral vessel wall, although its exact role in CAA pathogenesis remains unclear. Tissue transglutaminase (tTG) is an enzyme capable of inducing both protein complexes and altered protein bioactivity via post-translational cross-linking.

Tissue transglutaminase in Alzheimer's disease: involvement in pathogenesis and its potential as a therapeutic target.

Protein misfolding and the formation of stable insoluble protein complexes by self-interacting proteins, in particular amyloid-β and tau protein, play a central role in the pathogenesis of Alzheimer's disease (AD). Unfortunately, the underlying mechanisms that trigger the misfolding of self-interacting proteins that eventually results in formation of neurotoxic dimers, oligomers, and aggregates remain unclear. Elucidation of the driving forces of protein complex formation in AD is of crucial importance for the development of disease-modifying therapies.

Tissue transglutaminase colocalizes with extracellular matrix proteins in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a key histopathological hallmark of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). CAA is characterized by amyloid-beta (Aβ) depositions and remodeling of the extracellular matrix (ECM) in brain vessels and plays an important role in the development and progression of both AD and HCHWA-D. Tissue transglutaminase (tTG) modulates the ECM by molecular cross-linking of ECM proteins.

Tissue transglutaminase: a novel therapeutic target in cerebral amyloid angiopathy.

Accumulation of amyloid-β (Aβ) in brain vessel walls, known as cerebral amyloid angiopathy (CAA), plays a key role in Alzheimer's disease pathogenesis. CAA might result from impaired transport of Aβ out of the brain. Although the mechanisms underlying reduced Aβ transport are largely unknown, thickening of basement membrane extracellular matrix (ECM) is likely involved.

Transglutaminase 1 and its regulator tazarotene-induced gene 3 localize to neuronal tau inclusions in tauopathies.

Alzheimer's disease (AD), progressive supranuclear palsy (PSP), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and Pick's disease (PiD) are commonly known as tauopathies. Neurodegeneration observed in these diseases is linked to neuronal fibrillary hyperphosphorylated tau protein inclusions. Transglutaminases (TGs) are inducible enzymes, capable of modifying conformational and/or structural properties of proteins by inducing molecular cross-links.

Small heat shock proteins induce a cerebral inflammatory reaction.

More than 80% of Alzheimer's disease (AD) patients have some degree of cerebral amyloid angiopathy (CAA). In addition to arteries and veins, capillaries can also be affected. Capillary CAA (capCAA), rather than CAA in larger vessels, is associated with flame-like amyloid-beta (Aβ) deposits that may extend beyond the vessel wall and radiate into the neuropil, a phenomenon also known as "dyshoric angiopathy.