Breaking News
March 26, 2019 - Attention, Seniors: Drink More Water and Head Off Disease
March 26, 2019 - Peptide shows promise for protecting kidneys from nephritis
March 26, 2019 - Scientists identify common genetic variants associated with post-stroke recovery
March 26, 2019 - Study finds link between menopause and changes in body composition
March 26, 2019 - Higher levels of sex hormones in older men related to lower biological age
March 26, 2019 - Research links participation in team sports to larger hippocampal volumes in children
March 26, 2019 - Cerveau announces research collaboration agreement with Eisai for novel tau imaging agent
March 26, 2019 - New technique measures frequency of sounds emitted from biological structures
March 26, 2019 - Removal of ‘zombie cells’ alleviates causes of diabetes in obese mice
March 26, 2019 - Women exposed to deepwater horizon oil spill continue to experience PTSD symptoms
March 26, 2019 - Shaping new treatments for tuberculosis
March 26, 2019 - Understanding genetic interactions holds key to new personalized therapies
March 26, 2019 - Nervous system relies on guidance cues for neuronal axons to reach destinations
March 26, 2019 - Altering gut microbiome may be potential treatment option for PCOS
March 26, 2019 - Moleculin Files with FDA for Expedited Approval Pathway for Annamycin
March 26, 2019 - GPs play pivotal role in ensuring success of new Faster Diagnosis Standard for Cancer
March 26, 2019 - New clues discovered to lung transplant rejection
March 26, 2019 - New study offers insight into development of delusions
March 26, 2019 - Children’s ball pits full of pathogenic microbes
March 26, 2019 - Exploring pathophysiological factors that link sleep problems and Alzheimer’s disease
March 26, 2019 - Walking downhill after meals can reduce bone resorption in postmenopausal women with diabetes
March 26, 2019 - USA LESS Issues Voluntary Nationwide Recall of LEOPARD Miracle Honey Due to Presence of Undeclared Sildenafil
March 26, 2019 - CT scan prior to spine fusion finds almost half of patients had undiagnosed osteoporosis
March 26, 2019 - After 2 Apparent Student Suicides, Parkland Grieves Again
March 25, 2019 - Inherited form of rickets improves more with new injectable medicine than conventional therapy
March 25, 2019 - Trastuzumab Tied to Higher Long-Term Risk for Heart Failure
March 25, 2019 - Personal context directly affects CPAP use
March 25, 2019 - Mosquito tracking key to preventing disease outbreaks
March 25, 2019 - Scientists Detect Hidden Signals from Beneficial Bacteria
March 25, 2019 - Treating women with thyroid antibodies with Levothyroxine do not increase live birth rate
March 25, 2019 - Brain area that only processes spoken, not written words identified
March 25, 2019 - Race and ethnicity influence fracture risk in diabetic patients
March 25, 2019 - Researchers report new regenerative medicine approach for treating osteoarthritis of the knee
March 25, 2019 - Exposure to dim light at night may contribute to spread of breast cancer to bones
March 25, 2019 - Benefits of osteoporosis treatment in postmenopausal women outweigh the perceived risks
March 25, 2019 - Researchers find evidence of Cryptosporidium parasite in Minnesota’s public water systems
March 25, 2019 - Three Clues to Raised Risk of Miscarriage
March 25, 2019 - Structured play helps toddlers self-regulate, altering their life course
March 25, 2019 - Translating horror into justice: Stanford psychiatrist advocates for human rights
March 25, 2019 - HORIBA Medical introduces D-Dimer reagent for Yumizen G hemostasis range
March 25, 2019 - Recurrent pregnancy loss may be caused by sperm DNA damage, finds study
March 25, 2019 - Special Collection tracks development of new diagnostic tests for tuberculosis
March 25, 2019 - Air Force develops genetic test to predict mental performance
March 25, 2019 - To abort or not to abort—making difficult choices alone
March 25, 2019 - Computer vision technology could aid ICU care by spotting movement
March 25, 2019 - IONTAS wins ‘Small Business of the Year’ category at Cambridge News Business Excellence Awards 2019
March 25, 2019 - First postpartum depression drug gets FDA nod
March 25, 2019 - Research Recognition Award will help improve lives of young people with absence epilepsy
March 25, 2019 - Bisphosphonates to treat osteoporosis appears to be beneficial for all women
March 25, 2019 - Time-restricted eating may prove to be a dietary intervention against breast cancer
March 25, 2019 - Researchers develop new augmented reality app to assess spatial memory
March 25, 2019 - Dolomite Bio releases new Drop-seq datasets for single-cell RNA sequencing
March 25, 2019 - Hemoglobin A1c blood test may underestimate prevalence of diabetes
March 25, 2019 - Immune system errors linked to development of childhood leukemia
March 25, 2019 - Eating leafy green vegetables may help maintain muscle strength and mobility
March 25, 2019 - BMA secures state-backed clinical negligence indemnity scheme for GP trainees
March 25, 2019 - Biohaven Announces Completion of Pre-NDA Meeting With FDA for Oral CGRP Receptor Antagonist Rimegepant
March 25, 2019 - Adding breakfast to classrooms may have a health downside
March 25, 2019 - She Was Dancing On The Roof And Talking Gibberish. A Special Kind Of ER Helped Her.
March 25, 2019 - KNAUER introduces new Sepapure FPLC columns and media for protein purification tasks
March 25, 2019 - Weight loss in obese migraine sufferers can improve their quality of life
March 25, 2019 - Exposure to particulate air pollution may lead to reduced sperm production
March 25, 2019 - Synthetic peptide appears to disrupt inflammation and protect kidneys from nephritis
March 25, 2019 - New guideline focuses on strategies to improve health of older adults with diabetes
March 25, 2019 - Study evaluates prescribing of preventive drugs at the end of life in older adults with cancer
March 25, 2019 - Radial or femoral approaches for PCI are equal in terms of survival in heart attack patients
March 25, 2019 - Study shows how some autoimmune diseases are more closely related than others
March 25, 2019 - Long term opioid medications impacts production of important hormones
March 25, 2019 - FDA Issues Complete Response Letter for Zynquista (sotagliflozin)
March 25, 2019 - CDC researchers report on trends in hospital breastfeeding policies
March 25, 2019 - States Push For Caregiver Tax Credits
March 25, 2019 - Females on ketogenic diet fail to show metabolic benefits in animal model
March 25, 2019 - Modulating stiffness of blood-forming stem cells could facilitate mobilization procedures
March 25, 2019 - Gene editing regulations to be tightened
March 25, 2019 - CPAP treatment can result in weight loss in people with sleep apnea and obseity
March 25, 2019 - Highly attractive businesswomen are considered less trustworthy ‘femmes fatales’
March 25, 2019 - Breast Density Categorization Varies With Screening Modality
March 25, 2019 - Researchers explore link between metal exposure and Parkinson’s symptoms
March 25, 2019 - Later meal timing may contribute to weight gain
March 25, 2019 - Around one in hundred people has autism spectrum condition in China
Link between tuberculosis and Parkinson’s disease discovered

Link between tuberculosis and Parkinson’s disease discovered

image_pdfDownload PDFimage_print
Link between tuberculosis and Parkinson’s disease discovered
Credit: The Francis Crick Institute

The mechanism our immune cells use to clear bacterial infections like tuberculosis (TB) might also be implicated in Parkinson’s disease, according to a new collaborative study led by scientists from the Francis Crick Institute and Newcastle University.

The findings, which are published in the EMBO Journal, provide a possible explanation of the cause of Parkinson’s disease and suggest that drugs designed to treat Parkinson’s might also work for TB.

Parkinson’s protein

The most common genetic mutation in Parkinson’s disease patients is in a gene called LRRK2, which makes the LRRK2 protein overactive.

Drugs that block LRRK2 are a promising new treatment for Parkinson’s, with a number of pharmaceutical companies developing drugs to target LRRK2 and clinical trials underway. But how overactive LRRK2 causes Parkinson’s and why LRRK2 blockers work was a mystery.

The biological causes of Parkinson’s remain largely unknown, making it more difficult to develop and improve treatments. Discovering a mechanism that causes Parkinson’s and how drugs affect it could significantly advance efforts to improve treatments.

Insights from TB

By studying what LRRK2 does in immune cells called macrophages that are infected with Mycobacterium tuberculosis (Mtb) – the bacterium that causes TB—researchers believe they have uncovered a potential cause of Parkinson’s.

Macrophages recognise and engulf Mtb securing it within tight-fitting internal compartments called phagosomes. Another part of the cell called the lysosome then fuses with the phagosome to destroy the bacterium inside.

Using a combination of different experimental approaches, the researchers found that LRRK2 prevents phagosomes from fusing with lysosomes in both human and mouse macrophages, making them less efficient at clearing bacteria. Deleting the LRRK2 gene or treating the cells with an LRRK2 blocker significantly reduced levels of Mtb.

These findings in cells were supported by experiments in mice. When the researchers deleted the gene for LRRK2 in mice, they found that they exhibited an enhanced early immune response to TB infection, and had significantly lower levels of Mtb in their lungs than control mice up to two weeks after infection.

“We think that this mechanism might also be at play in Parkinson’s disease, where abnormal masses of protein called ‘Lewy bodies’ build up in neurons in the brain and cause damage,” said Susanne Herbst, joint first author of the paper and postdoctoral fellow at the Crick.

The team suspect that LRRK2 might be preventing immune cells in the brain from degrading cell debris properly, leading to a build-up of protein in neurons that disrupts their function.

Susanne added: “By studying TB, we have found a possible explanation for why LRRK2 mutations are a genetic risk factor for Parkinson’s disease. It’s exciting when different fields of research connect up in unexpected ways like this!”

Co-senior author Matthias Trost, expert in proteomics and phagosome biology at Newcastle University, said: “Both our labs independently identified the main findings and this paper is a great example where sharing data and combining different technologies made the difference.

“Our data implies that the conserved machinery that cells use to destroy and degrade external particles such as bacteria and damaged neurons is an important target for drug discovery.”

Parkinson’s disease expert and co-author Patrick Lewis, Associate Professor in Cellular and Molecular Neuroscience at the University of Reading, said: “The dogma in the Parkinson’s field has been to focus almost exclusively on what is happening to neurons in the brain to make them degenerate. But over the last few years, there has been a growing appreciation of the integral role of other cells in the brain and particularly the immune system in keeping neurons healthy.

“This study reinforces why we should think more broadly about the events that cause neurodegeneration, and that some of the answers to Parkinson’s disease might come from immunology.”

Anetta Härtlova, joint first author and postdoctoral researcher at Newcastle University, said: “Our work neatly agrees with recent findings that the immune system plays a key role in Parkinson’s disease and other neurodegenerative diseases. Thus, targeting inflammatory responses will be a key goal of Parkinson’s disease therapy.”

New TB treatments

The findings also suggest that LRRK2 inhibitors could be a powerful new way of combating TB, which kills 1.67 million people every year.

“Drug-resistant TB is a serious emerging problem, and boosting the body’s own immune defence against TB is an important step in the battle against antibiotic resistant strains,” said Max Gutierrez, Group Leader at the Crick and co-senior author of the paper.

“LRRK2 inhibiting drugs are already being developed to treat Parkinson’s disease and in my lab we’re trying to see if we can repurpose them as a potential new TB therapy. This should be relatively straightforward because TB infects the lungs, so the LRRK2 inhibitors wouldn’t need to cross the blood-brain barrier like they do in Parkinson’s disease.”

The research paper ‘LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages’ is published in the EMBO Journal.


Explore further:
Parkinson’s gene initiates disease outside of the brain

More information:
Anetta Härtlova et al. LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages, The EMBO Journal (2018). DOI: 10.15252/embj.201798694

Journal reference:
EMBO Journal

Provided by:
The Francis Crick Institute

Tagged with:

About author

Related Articles