Peripheral-Central Neuroimmune Crosstalk in Parkinson's Disease: What Do Patients and Animal Models Tell Us?

Fuzzati-Armentero, Marie Thérèse; Cerri, Silvia; Blandini, Fabio

doi:10.3389/fneur.2019.00232

Cited by 55 publications

(50 citation statements)

References 251 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed IL-1β enhanced pain transduction and conduction via modulation of ion channels such as TRP ankyrin 1 (TRPA1), TRPV1, and Nav1.7. CCL2 also contributes to macrophage recruitment (104,149). Thus, these factors serve to perpetuate a feedback loop between neuronal sensitization and cytokine production during tissue injury or inflammation.…”

Section: Peripheral Nociceptor Terminalmentioning

confidence: 99%

Neuraxial Cytokines in Pain States

et al. 2020

View full text Add to dashboard Cite

A high-intensity potentially tissue-injuring stimulus generates a homotopic response to escape the stimulus and is associated with an affective phenotype considered to represent pain. In the face of tissue or nerve injury, the afferent encoding systems display robust changes in the input-output function, leading to an ongoing sensation reported as painful and sensitization of the nociceptors such that an enhanced pain state is reported for a given somatic or visceral stimulus. Our understanding of the mechanisms underlying this non-linear processing of nociceptive stimuli has led to our appreciation of the role played by the functional interactions of neural and immune signaling systems in pain phenotypes. In pathological states, neural systems interact with the immune system through the actions of a variety of soluble mediators, including cytokines. Cytokines are recognized as important mediators of inflammatory and neuropathic pain, supporting system sensitization and the development of a persistent pathologic pain. Cytokines can induce a facilitation of nociceptive processing at all levels of the neuraxis including supraspinal centers where nociceptive input evokes an affective component of the pain state. We review here several key proinflammatory and anti-inflammatory cytokines/chemokines and explore their underlying actions at four levels of neuronal organization: (1) peripheral nociceptor termini; (2) dorsal root ganglia; (3) spinal cord; and (4) supraspinal areas. Thus, current thinking suggests that cytokines by this action throughout the neuraxis play key roles in the induction of pain and the maintenance of the facilitated states of pain behavior generated by tissue injury/inflammation and nerve injury.

show abstract

Section: Peripheral Nociceptor Terminalmentioning

confidence: 99%

Neuraxial Cytokines in Pain States

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Neuroinflammation-mostly expressed as microglia activation-is clearly implicated in PD progression and accompanies dopaminergic cell death since the very early phase of the disease (Fuzzati-Armentero et al, 2019). GCase defects may substantially contribute to this phenomenon.…”

Section: Glucocerebrosidase and Neuroinflammationmentioning

confidence: 99%

Glucocerebrosidase Defects as a Major Risk Factor for Parkinson’s Disease

Avenali

Blandini

Cerri³

2020

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

Heterozygous mutations of the GBA1 gene, encoding for lysosomal enzyme glucocerebrosidase (GCase), occur in a considerable percentage of all patients with sporadic Parkinson's disease (PD), varying between 8% and 12% across the world. Genome wide association studies have confirmed the strong correlation between PD and GBA1 mutations, pointing to this element as a major risk factor for PD, possibly the most important one after age. The pathobiological mechanisms underlying the link between a defective function of GCase and the development of PD are still unknown and are currently the focus of intense investigation in the community of pre-clinical and clinical researchers in the PD field. A major controversy regards the fact that, despite the unequivocal correlation between the presence of GBA1 mutations and the risk of developing PD, only a minority of asymptomatic carriers with GBA1 mutations convert to PD in their lifetime. GBA1 mutations reduce the enzymatic function of GCase, impairing lysosomal efficiency and the cellular ability to dispose of pathological alpha-synuclein. Changes in the cellular lipidic content resulting from the accumulation of glycosphingolipids, triggered by lysosomal dysfunction, may contribute to the pathological modification of alpha-synuclein, due to its ability to interact with cell membrane lipids. Mutant GCase can impair mitochondrial function and cause endoplasmic reticulum stress, thereby impacting on cellular energy production and proteostasis. Importantly, reduced GCase activity is associated with clear activation of microglia, a major mediator of neuroinflammatory response within the brain parenchyma, which points to neuroinflammation as a major consequence of GCase dysfunction. In this present review article, we summarize the current knowledge on the role of GBA1 mutations in PD development and their phenotypic correlations. We also discuss the potential role of the GCase pathway in the search for PD biomarkers that may enable the development of disease modifying therapies. Answering these questions will aid clinicians in offering more appropriate counseling to the patients and their caregivers and provide future directions for PD preclinical research.

show abstract

“…Currently, there are symptom-relieving medications but no cure for the disease. The pathophysiological mechanisms are not completely known but it has been suggested that inflammation, oxidative stress, and other neurotoxic processes are involved [ 2 , 3 , 4 , 5 , 6 , 7 ]. Therefore, identification of modifiable risk factors, such as diet, that affect the risk of PD is of great importance.…”

Section: Introductionmentioning

confidence: 99%

Milk and Fermented Milk Intake and Parkinson’s Disease: Cohort Study

et al. 2020

View full text Add to dashboard Cite

Milk and fermented milk consumption has been linked to health and mortality but the association with Parkinson’s disease (PD) is uncertain. We conducted a study to investigate whether milk and fermented milk intakes are associated with incident PD. This cohort study included 81,915 Swedish adults (with a mean age of 62 years) who completed a questionnaire, including questions about milk and fermented milk (soured milk and yogurt) intake, in 1997. PD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers. Multivariable-adjusted hazard ratios were obtained from Cox proportional hazards regression models. During a mean follow-up of 14.9 years, 1251 PD cases were identified in the cohort. Compared with no or low milk consumption (<40 mL/day), the hazard ratios of PD across quintiles of milk intake were 1.29 (95% CI 1.07, 1.56) for 40–159 mL/day, 1.19 (95% CI 0.99, 1.42) for 160–200 mL/day, 1.29 (95% CI 1.08, 1.53) for 201–400 mL/day, and 1.14 (95% CI 0.93, 1.40) for >400 mL/day. Fermented milk intake was not associated with PD. We found a weak association between milk intake and increased risk of PD but no dose–response relationship. Fermented milk intake was not associated with increased risk of PD.

show abstract

Peripheral-Central Neuroimmune Crosstalk in Parkinson's Disease: What Do Patients and Animal Models Tell Us?

Cited by 55 publications

References 251 publications

Neuraxial Cytokines in Pain States

Neuraxial Cytokines in Pain States

Glucocerebrosidase Defects as a Major Risk Factor for Parkinson’s Disease

Milk and Fermented Milk Intake and Parkinson’s Disease: Cohort Study

Contact Info

Product

Resources

About