Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration

Figueiredo‐Pereira, Maria E.; Rockwell, Patricia; Schmidt-Glenewinkel, T.; Serrano, Peter A.

doi:10.3389/fnmol.2014.00104

Cited by 80 publications

(71 citation statements)

References 238 publications

(332 reference statements)

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“…Currently, neuroinflammation in physiopathogenesis of PD is a subject of debate [17, 18]. Evidence of autoimmune involvement in PD was recently discussed [19].…”

Section: Discussionmentioning

confidence: 99%

Parkinsonism and Sjögren’s Syndrome: A Fortuitous Association or a Shared Immunopathogenesis?

Kchaou

Ali

Hmida

et al. 2015

Case Reports in Medicine

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Background. The Sjögren Syndrome (SS) can include various manifestations of central nervous system impairment. Extrapyramidal signs are known to be very rare and unusually discovered on early onset in this pathology. Observation. A 46-year-old woman with a history of progressive Parkinsonism for 6 years and a normal brain magnetic resonance imaging was partially improved with levodopa therapy. The later discovery of a sicca syndrome led to performing of further investigations, which revealed the presence of anti-SSA antibodies and a sialoadenitis of grade 4 according to Chisholm's classification on labial salivary gland biopsy. The diagnosis of primary SS was established and the adjunction of corticotherapy has remarkably improved Parkinson's signs without use of other immunosuppressive agents. Conclusion. Based on these findings, we discuss the hypothesis of either a causal link between SS and Parkinsonism or a fortuitous association of two distinct pathologies with or without a shared immunopathogenesis.

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“…Currently, neuroinflammation in physiopathogenesis of PD is a subject of debate [17, 18]. Evidence of autoimmune involvement in PD was recently discussed [19].…”

Section: Discussionmentioning

confidence: 99%

Parkinsonism and Sjögren’s Syndrome: A Fortuitous Association or a Shared Immunopathogenesis?

Kchaou

Ali

Hmida

et al. 2015

Case Reports in Medicine

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“…As previously mentioned, CBD can positively allosterically modulate COX, and increased COX1 and COX2 activities are thought to play an important role in the development of neuroinflammation in several neurodegenerative disorders [93,215]. However, interpretation is complicated because COX enzymes can also metabolize docosahexaenoic acid/ eicosapentaenoic acid to the anti-inflammatory resolvins [216].…”

Section: Cbd Enzyme Targets In Neurodegenerationmentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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“…The ubiquitin-proteasome pathway, for example, is an intracellular mechanism that regulates degradation of both normal and abnormal proteins, and promotes normal cell growth and metabolism. This pathway may be impaired due to chronic inflammation following TBI, resulting in inability to clear proteins such as Aβ and pTau efficiently 29 . The combination of abnormal protein deposition and reduced degradation and clearance abilities suggest plausible mechanisms linking single-event moderate to severe TBI to neurodegenerative processes.…”

Section: Hypotheses Linking Tbi To Progressive Neurodegenerative Diseasementioning

confidence: 99%

Injury cascades in TBI-related neurodegeneration

DeKosky

Asken

2017

Brain Injury

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Traumatic brain injury (TBI) is a widely-recognized risk factor for neurodegenerative disease. The purpose of this review is to provide an update on the state of the science related to injury cascades in TBI-related neurodegeneration. Acute and chronic pathological outcomes of TBI are similar to those seen in several neurodegenerative conditions, suggesting common linking pathways. Initial research described severe TBI patients with postmortem identification of abnormal proteins, such as amyloid deposits. History of mild TBI (mTBI) is less consistently associated with heightened risk of neurodegenerative outcomes, but specific populations with complicated medical histories and comorbidities may be more susceptible. Our understanding of a pathological signature associated with repetitive mTBI and/or subclinical brain trauma advanced significantly over the past decade, and is now commonly referred to as chronic traumatic encephalopathy. We discuss hypotheses linking TBI to neurodegenerative disease, and the importance of considering factors like injury severity, timing of injury (early life versus older age), injury frequency, and repetitive subclinical brain trauma when extrapolating results from current literature to certain populations. We describe the challenges to obtaining the data necessary for accurate epidemiological research and determination of true risk magnitude, and note the importance of developing treatment-based approaches to risk mitigation.

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Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration

Cited by 80 publications

References 238 publications

Parkinsonism and Sjögren’s Syndrome: A Fortuitous Association or a Shared Immunopathogenesis?

Parkinsonism and Sjögren’s Syndrome: A Fortuitous Association or a Shared Immunopathogenesis?

Molecular Targets of Cannabidiol in Neurological Disorders

Injury cascades in TBI-related neurodegeneration

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