1,721,625 research outputs found
Combination of cerebrospinal fluid determination of α-synuclein total tau, phosphorylated tau and β amyloid 1-42 for improving diagnostic accuracy of neurodegenerative disorders
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Regulation of Corticostriatal Synaptic Plasticity in Physiological and Pathological Conditions
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Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction
No full textAlthough the discovery of the critical role of alpha-synuclein (alpha-syn) in the pathogenesis of Parkinson's disease (PD) is now twenty-five years old, it still represents a milestone in PD research. Abnormal forms of alpha-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other alpha-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, alpha-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of alpha-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting alpha-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies
The putative role of neuroinflammation in the complex pathophysiology of migraine: From bench to bedside
No full textThe implications of neurogenic inflammation and neuroinflammation in the pathophysiology of migraine have been clearly demonstrated in preclinical migraine models involving several sites relevant in the trigemino-vascular system, including dural vessels and trigeminal endings, the trigeminal ganglion, the trigeminal nu-cleus caudalis as well as central trigeminal pain processing structures. In this context, a relevant role has been attributed over the years to some sensory and parasympathetic neuropeptides, in particular calcitonin gene neuropeptide, vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Several preclinical and clinical lines of evidence also support the implication of the potent vasodilator and messenger molecule nitric oxide in migraine pathophysiology. All these molecules are involved in vasodilation of the intracranial vasculature, as well as in the peripheral and central sensitization of the trigeminal system. At meningeal level, the engagement of some immune cells of innate immunity, including mast-cells and dendritic cells, and their mediators, has been observed in preclinical migraine models of neurogenic inflammation in response to sensory neuropeptides release due to trigemino-vascular system activation. In the context of neu-roinflammatory events implicated in migraine pathogenesis, also activated glial cells in the peripheral and central structures processing trigeminal nociceptive signals seem to play a relevant role. Finally, cortical spreading depression, the pathophysiological substrate of migraine aura, has been reported to be associated with inflammatory mechanisms such as pro-inflammatory cytokine upregulation and intracellular signalling. Reactive astrocytosis consequent to cortical spreading depression is linked to an upregulation of these inflammatory markers. The present review summarizes current findings on the roles of immune cells and inflammatory re-sponses in the pathophysiology of migraine and their possible exploitation in the view of innovative disease -modifying strategies
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