Brain-wide pathway for waste clearance captured by contrast enhanced MRI

Helene Benveniste of Stony Brook University discusses the use of contrast-enhanced MRI to visualize the glymphatic system, a paravascular pathway that facilitates the clearance of waste and solutes from the cerebrospinal fluid and interstitial fluid of the brain. Highlights:

• Glymphatic pathway function can be measured using dynamic contrast-enhanced MRI.
• Benveniste and colleagues used whole brain imaging to identify /confirm key features of the glymphatic pathway in rats.
• Many degenerative brain diseases are associated with the accumulation of proteins that form plaques (ie. Alzheimer’s disease). Clearance of these proteins is mediated by the glymphatic system.
• Contrast-enhanced MRI could potentially be used to evaluate 

iRHOM2 is a critical pathogenic mediator of inflammatory arthritis

Jane Salmon, Carl Blobel, Priya Darshinee Issuree, and Thorsten Maretzky of the Weill Cornell University Hospital for Special Surgery discuss the role of iRHOM2 in inflammatory arthritis. Highlights:

• TNF-α has been implicated in the pathology of rheumatoid arthritis (RA) and other inflammatory diseases. RA patients are currently treated with TNF inhibitors, but these therapeutics have many deleterious side effects.
• iRHOM2 regulates the maturation of TACE, and enzyme that cleaves and releases TNF-α from the surface of myeloid cells that mediate inflammation during arthritis.
• Inactivation of the gene that encodes iRHOM2 (Rhbdf2) protects mice from inflammatory arthritis.
• These findings suggest that iRHOM2 could be a suitable therapeutic target for the treatment of RA.

CXCR5+ T helper cells mediate protective immunity against tuberculosis

Shabaana Khader of the University of Pittsburgh discusses the identification of immune parameters that distinguish active and latent TB infections. Highlights:

• One third of the world's population is infected with Mycobacterium tuberculosis; however, only 5-10% will develop active infections.
• Individuals with latent infections have a 10% lifetime risk of developing active tuberculosis. This risk increases to 10% per year in the presence of HIV infection. It is therefore important to identify immunologic features that distinguish active TB from latent.
• Granulomas are immune cell aggregates that are a hallmark of TB infection. They play a protective role in latent TB, but can promote infection during active TB.
• Using human, non-human primate, and mouse models of TB infection, Khader and colleagues identified a subset of T helper cells (CXCR5+) that are associated with protective granulomas in latent TB.
• These results identify a previously unexpected role for CXCR5 in the control of TB infection and could be used to improve TB vaccine strategies.

Deimination restores inner retinal visual function in murine demyelinating disease

Sanjoy Bhattarcharya and Vittorio Porciatti of the University of Miami discuss the role of deimination, a post-translational protein modification, in retinal function. Highlights:

• Demyelinating diseases, including multiple sclerosis, are frequently accompanied by vision loss.
• Deimination is a protein modification that is impaired in the retinas of patients with demyelinating disease.
• Using a rat model of demyelinating disease, the researchers demonstrated that loss of deimination impaired retinal function.
• Restoration of deimination restored neurite outgrowth and retinal function, suggesting that deimination could be a therapeutic target.

PSD-95 expression controls L-DOPA dyskinesia through dopamine D1 receptor trafficking

Erwan Bezard and Laurent Groc of the University of Bordeaux discuss the effects of the post-synaptic density protein PSD-95 on the development of levodopa-induced dyskinesia. Highlights:

• L-DOPA-induced dyskinesia (LID) is a major side effect of dopamine replacement therapy for Parkinson’s disease.
• LID is associated with changes in D1 dopamine receptor (D1R) interactions at the striatal synapses.
• Using rat and macaque models, Bezard, Groc, and colleagues demonstrated that the synaptic density protein PSD-95 alters the trafficking of D1R to the synapse.
• Loss of PSD-95 in the striatum reduces the development and severity of LID.