Rab32 connects ER stress to mitochondrial defects in MS

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Rab32 connects ER stress to mitochondrial defects in MS

Postby NHE » Tue Apr 25, 2017 3:25 am

Rab32 connects ER stress to mitochondrial defects in multiple sclerosis.
J Neuroinflammation. 2017 Jan 23;14(1):19.

    BACKGROUND: Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between the triggering of the unfolded protein response (UPR) and downstream mitochondrial dysfunction are poorly understood, the membranous contacts between the ER and mitochondria, called the mitochondria-associated membrane (MAM), could provide a functional link between these two mechanisms. Therefore, we investigated whether the guanosine triphosphatase (GTPase) Rab32, a known regulator of the MAM, mitochondrial dynamics, and apoptosis, could be associated with ER stress as well as mitochondrial dysfunction.

    METHODS: We assessed Rab32 expression in MS patient and experimental autoimmune encephalomyelitis (EAE) tissue, via observation of mitochondria in primary neurons and via monitoring of survival of neuronal cells upon increased Rab32 expression.

    RESULTS: We found that the induction of Rab32 and other MAM proteins correlates with ER stress proteins in MS brain, as well as in EAE, and occurs in multiple central nervous system (CNS) cell types. We identify Rab32, known to increase in response to acute brain inflammation, as a novel unfolded protein response (UPR) target. High Rab32 expression shortens neurite length, alters mitochondria morphology, and accelerates apoptosis/necroptosis of human primary neurons and cell lines.

    CONCLUSIONS: ER stress is strongly associated with Rab32 upregulation in the progression of MS, leading to mitochondrial dysfunction and neuronal death.

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Re: Rab32 connects ER stress to mitochondrial defects in MS

Postby frodo » Fri Apr 28, 2017 1:01 am

This is not the first time that I heard about mitochondria as the ultimate cause of MS. I remember that some time ago I read about them being the first event for the development of a lesion. Maybe there is some kind of interaction between them and B-cells.
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Re: Rab32 connects ER stress to mitochondrial defects in MS

Postby violin » Tue May 09, 2017 9:38 pm

You are lots more scientific than I. All I know is my doctor told me a lot about hyperbaric oxygen chambers helping regenerate mitochondrial DNA in the brain. He has me using a home chamber with room air only. I believe that's because this mild hbot is best for neurological conditions, at least mine.
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