Inflammation, Infectious Triggers, and Parkinson's Disease

Caggiu, Elisa; Arru, Giannina; Hosseini, Sepideh; Niegowska, Magdalena; Sechi, GianPietro; Zarbo, Ignazio Roberto; Sechi, Leonardo Antonio

doi:10.3389/fneur.2019.00122

Cited by 163 publications

(136 citation statements)

References 107 publications

(116 reference statements)

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“…Although mutations or deletions of Parkin or PINK1 cause Parkinson disease in humans, mice deficient in either PINK1 or Parkin do not display any related phenotype. However, accumulating evidence shows that Parkinson's disease is accompanied by immune responses that lead to an increase in serum levels of pro-inflammatory cytokines such as interleukin-6 (IL6), tumor necrosis factor alpha (TNFα), interleukin-1β (IL1B), and interferon gamma (IFNG) (Brodacki et al, 2008;Koziorowski et al, 2012;Lindqvist et al, 2012;Dzamko et al, 2015;Houser and Tansey, 2017;Caggiu et al, 2019). Consistently, the challenge of PINK1 or Parkin deficient mice with immunogenic stress leads to the onset of Parkinson diseaselike symptoms (Frank-Cannon et al, 2008;Sliter et al, 2018;Matheoud et al, 2019).…”

Section: Pink1 and Parkin-regulated Mitophagymentioning

confidence: 99%

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Guo

Kroemer

2020

Front. Cell Dev. Biol.

260

159

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Mitochondrial dysfunction constitutes one of the hallmarks of aging and is characterized by irregular mitochondrial morphology, insufficient ATP production, accumulation of mitochondrial DNA (mtDNA) mutations, increased production of mitochondrial reactive oxygen species (ROS) and the consequent oxidative damage to nucleic acids, proteins and lipids. Mitophagy, a mitochondrial quality control mechanism enabling the degradation of damaged and superfluous mitochondria, prevents such detrimental effects and reinstates cellular homeostasis in response to stress. To date, there is increasing evidence that mitophagy is significantly impaired in several human pathologies including aging and age-related diseases such as neurodegenerative disorders, cardiovascular pathologies and cancer. Therapeutic interventions aiming at the induction of mitophagy may have the potency to ameliorate these dysfunctions. In this review, we summarize recent findings on mechanisms controlling mitophagy and its role in aging and the development of human pathologies.

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Section: Pink1 and Parkin-regulated Mitophagymentioning

confidence: 99%

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Guo

Kroemer

2020

Front. Cell Dev. Biol.

260

159

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“…Evidence indicates the existence of a pathogenetic link between inflammatory responses, the immune system, and the onset and progression of PD. High levels of circulating inflammatory cytokines, T cell infiltration, and glial cell reactions represent common features in several variants of PD, and also in mouse models of PD (Labzin et al, 2018;Caggiu et al, 2019;Kumar, 2019). Mitochondrial damage triggers inflammatory responses that may cause selective loss of dopaminergic neurons, giving rise to a PD phenotype.…”

Section: Mitochondrial Dysfunction Inflammatory Responses and Immunementioning

confidence: 99%

Mitochondrial Homeostasis and Signaling in Parkinson’s Disease

Scorziello

Borzacchiello

Sisalli

et al. 2020

Front. Aging Neurosci.

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The loss of dopaminergic (DA) neurons in the substantia nigra leads to a progressive, long-term decline of movement and other non-motor deficits. The symptoms of Parkinson's disease (PD) often appear later in the course of the disease, when most of the functional dopaminergic neurons have been lost. The late onset of the disease, the severity of the illness, and its impact on the global health system demand earlier diagnosis and better targeted therapy. PD etiology and pathogenesis are largely unknown. There are mutations in genes that have been linked to PD and, from these complex phenotypes, mitochondrial dysfunction emerged as central in the pathogenesis and evolution of PD. In fact, several PD-associated genes negatively impact on mitochondria physiology, supporting the notion that dysregulation of mitochondrial signaling and homeostasis is pathogenically relevant. Derangement of mitochondrial homeostatic controls can lead to oxidative stress and neuronal cell death. Restoring deranged signaling cascades to and from mitochondria in PD neurons may then represent a viable opportunity to reset energy metabolism and delay the death of dopaminergic neurons. Here, we will highlight the relevance of dysfunctional mitochondrial homeostasis and signaling in PD, the molecular mechanisms involved, and potential therapeutic approaches to restore mitochondrial activities in damaged neurons.

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“…The involvement of inflammatory processes and the adaptive immune system in the pathophysiology of neurodegenerative diseases is supported by evidence from a variety of studies [277][278][279][280]. Thus, inflammatory responses may be involved in both regenerative and degenerative processes, e.g., in multiple sclerosis and Parkinson's disease (PD).…”

Section: Central Nervous System Diseasesmentioning

confidence: 99%

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Martı́nez

Juarranz

Gutiérrez‐Cañas

et al. 2019

IJMS

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The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.

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Inflammation, Infectious Triggers, and Parkinson's Disease

Cited by 163 publications

References 107 publications

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Mitochondrial Homeostasis and Signaling in Parkinson’s Disease

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

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