Enhanced glycolytic metabolism supports transmigration of brain-infiltrating macrophages in multiple sclerosis

The migration of leukocytes into the CNS drives the neuropathology of multiple sclerosis (MS). It is likely that this penetration utilizes energy resources that remain to be defined. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined that macrophages within the perivascular cuff of postcapillary venules are highly glycolytic, as manifested by strong expression of lactate dehydrogenase A (LDHA), which converts pyruvate to lactate. These macrophages expressed prominent levels of monocarboxylate transporter-4 (MCT-4), which is specialized in the secretion of lactate from glycolytic cells. The functional relevance of glycolysis was confirmed by siRNA-mediated knockdown of LDHA and MCT-4, which decreased lactate secretion and macrophage transmigration. MCT-4 was in turn regulated by EMMPRIN (also known as CD147), as determined through coexpression and co-IP studies and siRNA-mediated EMMPRIN silencing. The functional relevance of MCT-4–EMMPRIN interaction was confirmed by lower macrophage transmigration in culture using the MCT-4 inhibitor α-cyano-4-hydroxy-cinnamic acid (CHCA), a cinnamon derivative. CHCA also reduced leukocyte infiltration and the clinical severity of EAE. Relevance to MS was corroborated by the strong expression of MCT-4, EMMPRIN, and LDHA in perivascular macrophages in MS brains. These results detail the metabolism of macrophages for transmigration from perivascular cuffs into the CNS parenchyma and identify CHCA a...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

Related Links:

Including specialist pharmacists in  multidisciplinary care teams for patients with Parkinson’s disease and multiple sclerosis could help to avoid up to 2,500 emergency admissions to hospital each year, according to NHS England.
Source: The Pharmaceutical Journal - Category: Drugs & Pharmacology Source Type: research
M. Yassine For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS). Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses. Other viruses that ...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Lau AYL, Chan E, Lau KK, Mok V, Siu DYW, Lee R PMID: 31416982 [PubMed - in process]
Source: Hong Kong Medical Journal - Category: General Medicine Tags: Hong Kong Med J Source Type: research
Central neuropathic pain can be difficult to treat and, subsequently, cause a great amount of disability and distress to patients, which limits quality of life. Common etiologies include the following: stroke, spinal cord injury, multiple sclerosis, infection, vasculitis, and malignancy. This case is a description of an 18-yr-old male patient diagnosed with a grade IV diffuse glioma who experienced severe neuropathic pain refractory to first-line treatment options including the following: gabapentinoids, tricyclic antidepressants, and selective serotonin and norepinephrine reuptake inhibitors. The patient remained on high-...
Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Case Report Source Type: research
Conclusions Six months of exercise provided benefits on lower urinary tract symptoms and quality of life in women with multiple sclerosis. Electrical stimulation potentiated the improvement on perineal musculature and quality of life. This trial was registered prospectively with the Clinical Trials Register, ID: BR-287q65 (http://www.ensaiosclinicos.gov.br/rg/RBR-287q65/).
Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Original Research Articles Source Type: research
ConclusionThere is some evidence that long-term treatment with interferon beta reduces the risk of EDSS 6.0 and SPMS compared to no treatment or placebo. More work is needed on the effect of second generation DMT and the relative effect of DMT on health outcomes.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Publication date: Available online 15 August 2019Source: Multiple Sclerosis and Related DisordersAuthor(s): Simona Lattanzi, Francesco Logullo, Claudia Cagnetti, Paolo Di Bella, Mauro Silvestrini
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
ConclusionThis small pilot study provides preliminary proof-of-concept data supporting low-intensity upper limb and breathing exercise programme for potential reduction of pain and improvement of functional independence in both ambulatory and non-ambulatory individuals with MS in a larger sample and that strengthening the upper limbs might be an additional pain relief mechanism.Trial registrationNTC03222596
Source: Neurological Sciences - Category: Neurology Source Type: research
New research finds that improving cholesterol levels by adopting a diet high in vegetables reduces exhaustion in people with multiple sclerosis.
Source: Health News from Medical News Today - Category: Consumer Health News Tags: Multiple Sclerosis Source Type: news
More News: Biomedical Science | Brain | Cinnamon | Diets | Multiple Sclerosis | Neurology | Nutrition | Study