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Scientists have long suspected that mitochondria, the energy-creating "powerhouse" of the cell, plays a link in causing multiple sclerosis.

Using human brain tissue samples, researchers at the Universities of Exeter and Alberta found a protein called Rab32 is present in large quantities in the brains of people with MS - but is virtually absent in healthy brain cells.

Where Rab32 is present, the team discovered that a part of the cell which stores calcium gets too close to the mitochondria.

The resulting miscommunication with the calcium supply triggers the mitochondria to misbehave, ultimately causing toxicity for brain cells in people with MS.

Researchers do not yet know what causes an unwelcome influx of Rab32 but they believe the defect could originate at the base of the cell.

• 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.

NHE wrote:

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

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