Good news! This research indicates possible new treatment options!
"... Researchers... recently carried out a mouse study investigating the possible contribution of a specific molecular process that leads to cell death, called parthanatos, in the loss of neurons resulting from neuroinflammation, such as that associated with MS. Their findings ... suggest that damage to neurons associated with MS is caused by immune responses that trigger internal cell death programs. ...
The researchers subsequently blocked the final stage of parthanatos using genetic pharmacological approaches to inhibit MIF nuclease activity. MIF nuclease is the enzyme responsible for DNA damage in parthanathos. Remarkably, they found that blocking this enzyme reduced DNA fragmentation, led to the survival of more neurons and significantly lowered the severity of the symptoms presented by mice. ..."
From the abstract:
"Central nervous system inflammation is implicated in neurodegeneration across several disorders, including multiple sclerosis (MS). While marked therapeutic progress has been made in preventing relapses in MS, primary neuroprotection in this disease remains elusive. This, in part, is due to an incomplete understanding of the molecular pathways involved in immune-mediated neuronal death.
Here we show that parthanatos, a recently described caspase-independent and DNA damage-induced cell death program, contributes to neuron death in the experimental autoimmune encephalomyelitis (EAE) mouse model of autoimmune neuroinflammation.
We reveal that DNA damage increases in neurons during EAE, and that neurons are progressively lost over the disease course. Neurons in affected areas display intracellular hallmarks of the parthanatos cascade.
Genetic or pharmacologic blockade of the final step in parthanatos, genomic fragmentation by macrophage migration inhibitory factor (MIF) nuclease, reduces neuron loss and disease severity.
Transcriptomic characterization of neurons with and without MIF nuclease activity reveals parthanatos-dependent differences in response to EAE. Together, this work establishes parthanatos as a key mechanism of neuron cell death during neuroinflammation."
Autoimmune neuroinflammation leads to neuronal death via MIF nuclease-mediated parthanatos (open access)
Fig. 2: Accumulation of parthanatos markers in lumbar spinal cord neurons during EAE.
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