promotes brain inflammation without overt neurodegeneration and could decrease the amount of amyloid plaques while increasing tau hyperphosphorylation in 3xTgAD/IL-1βXAT mice. The fibrillar form of is recognised by TLR2 and also activates the NLRP3 α-synuclein inflammasome leading to the release of IL-1β from human monocytes, as opposed to the monomer form which does not. The activation of NLRP3 is triggered by lysosomal rupture induced by the phagocytosis of fibrils both in isolated monocytes and in monocytic α-synuclein and neuronal cell lines, . The activation of NLRP3 in dopaminergic neurons in the substantia nigra of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced or transgenic mouse models of PD depends largely on Cdk5, as inhibition or deletion of Cdk5 efficiently blocks NLRP3 and neuroinflammation in these models. Thus, inflammasome-mediated actions are linked with several major pathological changes in neurodegenerative diseases and hence represent a promising therapeutic target. Local and systemic inflammatory signals interact in brain disease Complex interactions between peripheral and central inflammasome-mediated pathways, involving diverse stimuli such as the microbiota, tissue injury and metabolic alterations, could contribute to neuroinflammation and neurodegenerative diseases. Understanding these mechanisms will be instrumental to support both diagnosis and treatment. For example, type 2 diabetes is identified as a risk factor for AD and for cerebrovascular disease in general, , . Amyloid deposits (misfolded proteins rich in cross-β-sheet structure, which accumulate in various tissues in the form of plaques) are a hallmark of AD, but they are also typical in type 2 diabetes as islet amyloid polypeptide (IAPP) in the pancreas. Bacteria also produce amyloids as a component of their extracellular matrix during biofilm formation. Curli fibers produced by
promotes brain inflammation without overt neurodegeneration and could decrease the amount of amyloid plaques while increasing tau hyperphosphorylation in 3xTgAD/IL-1βXAT mice. The fibrillar form of α-synuclein is recognised by TLR2 and also activates the NLRP3 inflammasome leading to the release of IL-1β from human monocytes, as opposed to the monomer form which does not. The activation of NLRP3 is triggered by lysosomal rupture induced by the phagocytosis of α-synuclein fibrils both in isolated monocytes and in monocytic and neuronal cell lines, . The activation of NLRP3 in dopaminergic neurons in the substantia nigra of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced or transgenic mouse models of PD depends largely on Cdk5, as inhibition or deletion of Cdk5 efficiently blocks NLRP3 and neuroinflammation in these models. Thus, inflammasome-mediated actions are linked with several major pathological changes in neurodegenerative diseases and hence represent a promising therapeutic target. Local and systemic inflammatory signals interact in brain disease Complex interactions between peripheral and central inflammasome-mediated pathways, involving diverse stimuli such as the microbiota, tissue injury and metabolic alterations, could contribute to neuroinflammation and neurodegenerative diseases. Understanding these mechanisms will be instrumental to support both diagnosis and treatment. For example, type 2 diabetes is identified as a risk factor for AD and for cerebrovascular disease in general, , . Amyloid deposits (misfolded proteins rich in cross-β-sheet structure, which accumulate in various tissues in the form of plaques) are a hallmark of AD, but they are also typical in type 2 diabetes as islet amyloid polypeptide (IAPP) in the pancreas. Bacteria also produce amyloids as a component of their extracellular matrix during biofilm formation. Curli fibers produced by