Significance: Accumulating evidence suggests that inflammation is a major contributor in the pathogenesis of several highly prevalent, but also rare, neurological diseases. In particular, the neurodegenerative processes of Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease (PD), and multiple sclerosis (MS) are fueled by neuroinflammation, which, in turn, is accompanied by a parallel systemic immune dysregulation. This cross-talk between periphery and the brain becomes substantial when the blood-brain barrier loses its integrity, as often occurs in the course of these diseases. It has been hypothesized that the perpetual bidirectional flux of inflammatory mediators is not a mere "static"collateral effect of the neurodegeneration, but represents a proactive phenomenon sparking and driving the neuropathological processes. However, the upstream/downstream relationship between inflammatory events and neurological pathology is still unclear. Recent Advances: Solid recent evidence clearly suggests that metabolic factors, systemic infections, Microbiota dysbiosis, and oxidative stress are implicated, although to a different extent, in the development in brain diseases. Critical Issues: Here, we reviewed the most solid published evidence supporting the implication of the axis systemic inflammation-neuroinflammation-neurodegeneration in the pathogenesis of AD, VAD, PD, and MS, highlighting the possible cause of the putative downstream component of the axis. Future Directions: Reaching a definitive clinical/epidemiological appreciation of the etiopathogenic significance of the connection between peripheral and brain inflammation in neurologic disorders is pivotal since it could open novel therapeutic avenues for these diseases.

Inflammation in Neurological Disorders: The Thin Boundary between Brain and Periphery

Cervellati C.
Primo
;
Trentini A.
Secondo
;
Pecorelli A.
Penultimo
;
Valacchi G.
Ultimo
2020

Abstract

Significance: Accumulating evidence suggests that inflammation is a major contributor in the pathogenesis of several highly prevalent, but also rare, neurological diseases. In particular, the neurodegenerative processes of Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease (PD), and multiple sclerosis (MS) are fueled by neuroinflammation, which, in turn, is accompanied by a parallel systemic immune dysregulation. This cross-talk between periphery and the brain becomes substantial when the blood-brain barrier loses its integrity, as often occurs in the course of these diseases. It has been hypothesized that the perpetual bidirectional flux of inflammatory mediators is not a mere "static"collateral effect of the neurodegeneration, but represents a proactive phenomenon sparking and driving the neuropathological processes. However, the upstream/downstream relationship between inflammatory events and neurological pathology is still unclear. Recent Advances: Solid recent evidence clearly suggests that metabolic factors, systemic infections, Microbiota dysbiosis, and oxidative stress are implicated, although to a different extent, in the development in brain diseases. Critical Issues: Here, we reviewed the most solid published evidence supporting the implication of the axis systemic inflammation-neuroinflammation-neurodegeneration in the pathogenesis of AD, VAD, PD, and MS, highlighting the possible cause of the putative downstream component of the axis. Future Directions: Reaching a definitive clinical/epidemiological appreciation of the etiopathogenic significance of the connection between peripheral and brain inflammation in neurologic disorders is pivotal since it could open novel therapeutic avenues for these diseases.
2020
Cervellati, C.; Trentini, A.; Pecorelli, A.; Valacchi, G.
File in questo prodotto:
File Dimensione Formato  
Cervellati et al., 2020 ARS.pdf

solo gestori archivio

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 573.93 kB
Formato Adobe PDF
573.93 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
ars.2020.8076.pdf

accesso aperto

Descrizione: Post-print
Tipologia: Post-print
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 959.17 kB
Formato Adobe PDF
959.17 kB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2422958
Citazioni
  • ???jsp.display-item.citation.pmc??? 40
  • Scopus 80
  • ???jsp.display-item.citation.isi??? 76
social impact