Inflammation, apoptosis and autophagy as critical players in vascular dementia:
Vascular dementia is the second-most cause of dementia, characterized by cerebral infarcts, white matter lesions, myelin loss and often amyloid angiopathy. Hence, vascular damage is a critical cause of neuronal loss and synaptic disintegration. Abnormal neuroinflammation, autophagy and apoptosis are the prerequisite factors for endothelial and neuronal cell damage. This leads to the onset and progression of cerebrovascular disorders and cognitive dysfunction. The innate immune cells, pattern recognition receptors, Toll-like receptor-4 and related inflammatory mechanisms disrupt cerebrovascular integrity via glial activation and increased pro-inflammatory interleukins and TNFα. Inflammasome polymorphisms and multi-faceted neuro-immune interactions further integrate systemic and central inflammatory pathways, which induce vascular tissue injury and neurodegeneration. Specifically, chronic cerebral hypoperfusion disrupts the self-cannibalization mechanism of autophagy via altered expression of autophagy-specific proteins, Beclin-1, LC3 and P62. The deregulated autophagy pathway causes neuronal loss, hippocampal shrinkage, and ultimate loss in synaptic plasticity. The vascular dementia models typically exhibit downregulated anti-apoptotic Bcl-2 and upregulated pro-apoptotic Bax, cleaved caspase-3, and cleaved-PARP levels in the brain, for which modulated p38 MAPK and JNK phosphorylation pathways play a vital role. Endoplasmic stress-induced apoptosis, calcium overload and glutamate excitotoxicity in combination with ASK1-MAPK signaling mechanism also contribute to the cerebrovascular pathology. Vascular injury reduces neurological scores and increases the infarct volume, DNA damage and neuronal apoptosis in ischemia/reperfusion injury. Additionally, synergistic and additive interactions between inflammasome, autophagy and apoptotic signaling pathways augment symptoms of vascular neurodegeneration. Overall, the current review enlightens the key risk factors and underlying mechanism triggering vascular dementia. The review additionally informs the challenges associated while treating vascular dysfunction, and highlights the need for targeted drugs for reducing cerebrovascular damage.
L'articolo Inflammation, apoptosis and autophagy as critical players in vascular dementia sembra essere il primo su European Review.
Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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- Treatment of rheumatic immune-related adverse even...
- Triapine.
- Localized Extra-pulmonary Small Cell Carcinoma (EP...
- Obesity on voriconazole pharmacokinetics
- Investigate coagulation disturbance with viscoelas...
- Nodal recurrences after stereotactic body radiothe...
- Liquid biopsy for ALK-positive early non-small-cel...
- Immune checkpoint inhibitors in clinical diagnosis...
- Childhood Anaplastic Large Cell Lymphoma
- Injection laryngoplasty for treatment of congenita...
- TGF-β and Eomes control the homeostasis of CD8+ re...
- Cell Cycle
- Inhibition of Nuclear Pore Complex Formation Selec...
- Azidothymidine (AZT) Inhibits Proliferation of Hum...
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- Mutations in the stromal antigen 3 (STAG3) gene ca...
- Low C6orf141 Expression in Oral Cancer.
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- Tracheopulmonary Complications of a Malpositioned ...
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- STAT1 deficiency predisposes to spontaneous otitis...
- Identifying risk factors for the prognosis of head...
- Orbital Involvement by Biphenotypic Sinonasal Sarcoma
- Association between treatment package time and cli...
- Herpesvirus Epigenetic Reprogramming and Oncogenesis.
- Epidemiologic factors in patients with advanced he...
- Improved nutritional support with immune-modulatin...
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- Pros and Cons of the Exoscope for Otologic Surgery.
- Postoperative Oral Corticosteroids Improve Results...
- Intestinal flora in patients with chronic rhinosin...
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- The synergy of germline C634Y and V292M RET mutati...
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- Comparison of transnasal and transoral routes of m...
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- Effect of topical swallowed steroids on the bacter...
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- Timed barium swallow for assessing long‐term treat...
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