• Iron In Multiple System Atrophy

    From ironjustice@21:1/5 to All on Tue Jan 30 06:43:48 2018
    The Relevance of Iron in the Pathogenesis of Multiple System Atrophy: A Viewpoint.
    Kaindlstorfer C1, Jellinger KA2, Eschlböck S1, Stefanova N1, Weiss G3, Wenning GK1.
    J Alzheimers Dis. 2018;61(4):1253-1273. doi: 10.3233/JAD-170601.

    Iron is essential for cellular development and maintenance of multiple physiological processes in the central nervous system. The disturbance of its homeostasis leads to abnormal iron deposition in the brain and causes neurotoxicity via generation of
    free radicals and oxidative stress. Iron toxicity has been established in the pathogenesis of Parkinson's disease; however, its contribution to multiple system atrophy (MSA) remains elusive. MSA is characterized by cytoplasmic inclusions of misfolded α-
    synuclein (α-SYN) in oligodendrocytes referred to as glial cytoplasmic inclusions (GCIs). Remarkably, the oligodendrocytes possess high amounts of iron, which together with GCI pathology make a contribution toward MSA pathogenesis likely. Consistent
    with this observation, the GCI density is associated with neurodegeneration in central autonomic networks as well as olivopontocerebellar and striatonigral pathways. Iron converts native α-SYN into a β-sheet conformation and promotes its aggregation
    either directly or via increasing levels of oxidative stress. Interestingly, α-SYN possesses ferrireductase activity and α-SYN expression underlies iron mediated translational control via RNA stem loop structures. Despite a correlation between
    progressive putaminal atrophy and iron accumulation as well as clinical decline, it remains unclear whether pathologic iron accumulation in MSA is a secondary event in the cascade of neuronal degeneration rather than a primary cause. This review
    summarizes the current knowledge of iron in MSA and gives evidence for perturbed iron homeostasis as a potential pathogenic factor in MSA-associated neurodegeneration.

    Iron; Parkinson’s disease; multiple system atrophy; neurodegeneration; α-SYN

    PMID: 29376857 DOI: 10.3233/JAD-170601

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  • From ironjustice@21:1/5 to All on Tue Oct 5 09:47:16 2021
    Targeting brain iron in multiple system atrophy offers therapeutic potential
    by Florey Institute of Neuroscience and Mental Health
    SEPTEMBER 30, 2021

    Researchers from the Florey Institute of Neuroscience and Mental Health have advanced understanding of the biological mechanisms underlying a rare neurological disease called Multiple System Atrophy (MSA), finding evidence of brain iron accumulation in
    animal models of the condition. The team's work opens new pathways to investigate and advance therapeutic options in MSA that target iron overload in the brain.

    Led by Dr. Jay Shukla, Prof David Finkelstein and team, new research published in the journal Neurobiology of Disease marks the first study to demonstrate elevated brain iron levels in mice with MSA.

    "Using a research model, we were able to target and reduce brain iron levels using a known iron-lowering compound. Excitingly, our results showed that the compound slowed neurodegeneration and prevented symptom progression in mice giving us confidence
    that we're on the right track in understanding more about treating this disease," said Dr. Shukla.

    While scientists have identified high levels of brain iron in people affected by multiple system atrophy through post-mortem studies, the role of iron in disease progression and the question of whether reducing iron levels could help improve MSA disease
    symptoms has remained unanswered.

    "What we believe may be contributing to elevated brain iron levels in multiple system atrophy is dysfunction of an enzyme that plays a role in the body's iron metabolism. Targeting this enzyme and accumulated iron stores may prove a viable therapeutic
    strategy," Dr. Shukla explained.

    Multiple system atrophy is a degenerative, parkinsonian condition affecting movement, breathing, blood pressure and other body functions. Around 3,000 people in Australia live with the condition.

    No disease-modifying therapies are currently available to treat the condition. The average prognosis after receiving a diagnosis of MSA is currently less than ten years, hence treatment options are desperately needed.

    "For people living with multiple system atrophy and their families and carers, we hope this research and the work we are continuing to do in MSA at the Florey Institute sends a message of hope," said Prof Finkelstein, Head of the Parkinson's Disease
    Laboratory at the Florey Institute.

    "We are constantly making progress in learning more about this rare disorder and working to find new treatment pathways to improve the lives of those who are affected," he added.

    "This exciting project by the team at Florey Institute is a great example of the excellent work supported by the Multiple System Atrophy Coalition's research grant program. Given our goal to seed fund the development of disease-modifying therapies which
    can slow, stop or reverse the progression of MSA, the new evidence presented in this paper gives us hope that a successful therapeutic strategy for MSA may be in reach," commented Pam Bower, Board of Directors from The Multiple System Atrophy Coalition.

    Explore further

    Physical exercise modulates iron in Alzheimer's disease
    More information: Jay J. Shukla et al, Therapeutic potential of iron modulating drugs in a mouse model of multiple system atrophy, Neurobiology of Disease (2021). DOI: 10.1016/j.nbd.2021.105509
    Journal information: Neurobiology of Disease
    Provided by Florey Institute of Neuroscience and Mental Health

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