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

87Citations
Citations of this article
176Readers
Mendeley users who have this article in their library.

Abstract

The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation) may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia, and prion diseases. Cyclooxygenases (COX-1 and COX-2), which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1) exert their actions, (2) potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3) disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4) contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury (TBI), and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects.

References Powered by Scopus

Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice

3847Citations
N/AReaders
Get full text

Prostaglandins and leukotrienes: Advances in eicosanoid biology

3264Citations
N/AReaders
Get full text

Mechanisms Underlying Inflammation in Neurodegeneration

2953Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Neuroinflammation in Alzheimer's disease: Current evidence and future directions

1269Citations
N/AReaders
Get full text

Molecular Targets of Cannabidiol in Neurological Disorders

452Citations
N/AReaders
Get full text

Oxidized cholesterol as the driving force behind the development of Alzheimer's disease

157Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Figueiredo-Pereira, M. E., Rockwell, P., Schmidt-Glenewinkel, T., & Serrano, P. (2015, January 13). Neuroinflammation and J2 prostaglandins: Linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration. Frontiers in Molecular Neuroscience. Frontiers Media S.A. https://doi.org/10.3389/fnmol.2014.00104

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 66

67%

Researcher 20

20%

Professor / Associate Prof. 11

11%

Lecturer / Post doc 1

1%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 27

29%

Biochemistry, Genetics and Molecular Bi... 27

29%

Medicine and Dentistry 25

27%

Neuroscience 13

14%

Article Metrics

Tooltip
Mentions
Blog Mentions: 1
News Mentions: 1
Social Media
Shares, Likes & Comments: 7

Save time finding and organizing research with Mendeley

Sign up for free