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Tauopathy is neuropathological finding associated with Alzheimer's disease. A new study from a group of researchers at the MD Anderson Cancer Center suggests that the neurotoxic side effects of the chemotherapy agent cisplatin accelerates formation of Tau-1 clusters and decreases levels of the post-synaptic marker PSD95 and of the presynaptic marker synaptophysin in the hippocampus. These findings demonstrate for the first time that certain neurotoxic chemotherapy agents can accelerate development of tauopathy and loss of synaptic integrity in the hippocampus. This finding demonstrates how neurotoxic chemicals can modify the subclinical and clinical course of a neurodegenerative disease associated with memory dysfunction. These results are of importance to patients diagnosed with cancer who also have a family history of Alzheimer's disease. If you have any concerns about these findings please discuss these with your treating physician.
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A new study by Harischandra and colleagues which appear in Science Signaling suggests that manganese promotes the aggregation and prion-like cell-to-cell exosomal transmission of α-synuclein which is implicated in Parkinson's disease. Welders exposed to manganese were found to have increased misfolded α-synuclein in their serum exosomes.
These novel findings shed light on a previously unrecognized mechanism via which manganese can exacerbate and unmask latent idiopathic Parkinson's disease.
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A study by Goutman and colleagues which appears in the Journal of Neurology Neurosurgery and Psychiatry finds that higher plasma levels of persistent environmental pollutants is a risk factor in the progression of ALS.
These findings indicate that environmental exposures to toxicants plays a role in the progression of neurodegenerative disease such as ALS.
Link to original news report in Science Daily
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A new study by Carmona et al. (2019) suggests that a mutation in a gene (Slc30a10) implicated in familial forms of parkinsonism plays a role in the accumulation of manganese (Mn) within the golgi apparatus of cells. This gene encodes for a cell surface protein involved in the efflux of Mn which protects the cell against Mn toxicity. Mutations in this gene result in synthesis of a defective protein that does not does not function properly resulting in accumulation of Mn within the cell. Carmona and colleagues (2019) used a newly developed SXRF cryogenic nanoimaging technology to show that Mn gets trapped inside vesicles within the Golgi apparatus (see image below) suggesting that interactions between Mn and vesicular trafficking machinery may play a role in the parkinsonism.
Link to story in Physics World by Belle Dumé
Link to citation in PubMed
Welders have elevated serum levels of ASC and proinflammatory cytokines compared to age-matched controls.
Results of a new study by Sarkar and colleagues (2019) published in the journal Science Signaling suggests that exposure to constituents of welding fumes amplifies NLRP3 inflammasome signaling and exosomal ASC release. The NLRP3 inflammasome oligomeric complex is composed of an adapter protein ASC (apoptosis- associated speck-like protein containing a CARD), caspase-1, and NLRP3. Welders have plasma exosomes that contain more of the adapter protein ASC (apoptosis- associated speck-like protein containing a CARD) than controls. Many factors have been implicated in activation of the NLRP3 inflammasome cascade including mitochondrial dysfunction which can be mediated by manganese. However, when these investigators analyzed whole blood for manganese levels in welders and unexposed controls they did not observe any significant differences. More work is needed to determine which constituents of welding fumes are are associated with these observations.
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Researchers from Boston University School of Medicine (Ash et al., 2019) have reported on new data demonstrating a direct mechanistic link between exposure to heavy metals and risk for developing ALS. These studies showed that lead (Pb) and methyl mercury (MeHg) disrupt the homeostasis of TDP-43 in neurons. These metals also triggered the accumulation of insoluble TDP-43 in cultured cells and in the cortices of exposed mice. These new data provide evidence for a mechanistic link between a commonly cited environmental risk factor for ALS, and molecular changes in TDP-43, the primary pathological protein accumulating in ALS.
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Manganese exposure exacerbates progressive motor deﬁcits and neurodegeneration in the Mito Park mouse model of Parkinson’s disease.
A recently study by Langley and colleagues used the MitoPark mouse model of PD which recapitulates the behavioral symptoms and neuropathological changes associated with PD to investigate the effects of low level manganese exposure on disease progression. The study found that exposure to manganese (10 mg/kg, p.o. daily for 4 weeks) accelerated the rate of progression of motor deﬁcits in MitoPark mice and also enhanced oxidative damage in the striatum and substantia nigra (SN) of these mice. These new results provide additional data in the growing body of research indicating that neurotoxicants such as manganese that increase oxidative stress can augment mitochondrial dysfunction and exacerbate nigrostriatal neurodegeneration which in turn can unmask latent PD-related behavioral symptoms.
Link to citation in Pubmed
ScienceDaily is reporting on recent research from Glen Hanson and colleagues from the University of Utah showing that Attention Deficit Hyperactivity Disorder is associated with an increased risk for parkinsonism. The study found that patient's with ADHD were more likely to develop early onset parkinsonism than individuals of the same gender and age who did not have ADHD. The risk was dramatically increased, eight- to nine-fold among those ADHD patients who had a history of being treated with amphetamine-like drugs. This study adds to the growing body of literature implicating chemicals in a younger age at onset of Parkinson's disease and other forms of parkinsonism.
Link to story in ScienceDaily
Is it possible that people could be at greater risk for toxic effects when they are exposed to chemical mixtures than when they are exposed to the same chemicals at the same concentrations individually?
According to Professor Andreas Kortenkamp, of Brunel University "An increasing body of science shows a neglect of mixture effects can cause chemical risks to be underestimated". Regulators have long operated under the assumption that if the concentration of each chemical in a mixture does not exceed the recommended exposure limits, that risk for toxicity is low. But, when chemicals share common mechanisms of action they can produce additive or synergistic effects even at exposure leaves below current regulatory limits. The logic behind additive and synergistic effects on the central nervous system is best exemplified by the consequences of drinking alcohol after ingesting benzodiazepines. Since both chemicals act to enhance inhibitory neurotransmission, their combined effect on behavior and consciousness will be greater than that which occurs the same dose of either chemical alone. Physicians and toxicologists who work in Emergency Departments are well aware of this type of interaction. So why can't those involved in creating regulatory policies for chemical constituents of paints, solvents, and pesticides create policies that anticipate these same risks? The answer may be due in part to the fact that unlike alcoholic beverage and benzodiazepines, industrial solvents and pesticides are "not intended for human consumption" and because proper industrial hygiene practices are expected to be sufficient to reduced exposure to levels below the current occupational exposure limits.
Link to original story appearing in Medicalxpress
Dr. Marcia Ratner, discusses the role neurotoxic chemical exposures play in creating neurodiverse conditions, and gives tips on prevention and treatment options.
Link to Blog Post at DifferentBrains.org
Dr. Marcia Ratner shares and reviews the news.