Summary: Study implicates abnormalities in SOD1 with Parkinson’s disease and ALS.
Source: University of Sydney.
The discovery that the abnormal SOD1 protein is also linked to nerve cell loss in the Parkinson’s disease brain, suggests coincident degenerative pathways in Parkinson’s disease and ALS. NeuroscienceNews.com image is for illustrative purposes only. Credit: Emw.
Discovery may offer hope to Parkinson’s disease and ALS patients.
The finding of a common protein abnormality in these degenerative diseases supports a hypothesis among experts that abnormal deposition of proteins in many neurodegenerative disorders reflects an early change in these proteins.
“We have pinpointed a protein abnormality known as the ‘SOD1 fingerprint’ in regions of neuronal loss in the Parkinson’s disease brain,” said Associate Professor Kay Double who led the research published in Acta Neuropathologica.
“We believe this loss of neurons results from a combination of oxidative stress and a regional deficiency in copper, both of which occur specifically in vulnerable regions of the Parkinson’s disease brain.”
This new finding may offer hope to Parkinson’s disease patients, since therapies targeting abnormal SOD1 protein have resulted in substantial improvements in motor function and survival time in models of ALS, prompting their progression into human clinical trials in this disease. This new finding suggests that such therapies may also be useful to treat Parkinson’s disease.
The discovery that the abnormal SOD1 protein is also linked to nerve cell loss in the Parkinson’s disease brain, suggests coincident degenerative pathways in Parkinson’s disease and ALS.
Alterations in the anti-oxidant enzyme superoxide dismutase (SOD1) underlie around 20 percent of familial (f)ALS cases, where mutations to the sod1 gene result in functional and/or structural defects, including misfolding of the protein and loss of copper binding capacity. The aggregation of mutant SOD1 is believed to underlie motor neuron death in these ALS patients.
Source: Danielle Posthuma – University of Sydney
Original Research: Abstract for “Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson’s disease brain” by Benjamin G. Trist, Katherine M. Davies, Veronica Cottam, Sian Genoud, Richard Ortega, Stéphane Roudeau, Asuncion Carmona, Kasun De Silva, Valerie Wasinger, Simon J. G. Lewis, Perminder Sachdev, Bradley Smith, Claire Troakes, Caroline Vance, Christopher Shaw, Safa Al-Sarraj, Helen J. Ball, Glenda M. Halliday, Dominic J. Hare, and Kay L. Double in Acta Neuropathologica. Published online May 17 2017 doi:10.1007/s00401-017-1726-6
Abstract
Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson’s disease brain
Neuronal loss in numerous neurodegenerative disorders has been linked to protein aggregation and oxidative stress. Emerging data regarding overlapping proteinopathy in traditionally distinct neurodegenerative diseases suggest that disease-modifying treatments targeting these pathological features may exhibit efficacy across multiple disorders. Here, we describe proteinopathy distinct from classic synucleinopathy, predominantly comprised of the anti-oxidant enzyme superoxide dismutase-1 (SOD1), in the Parkinson’s disease brain. Significant expression of this pathology closely reflected the regional pattern of neuronal loss. The protein composition and non-amyloid macrostructure of these novel aggregates closely resembles that of neurotoxic SOD1 deposits in SOD1-associated familial amyotrophic lateral sclerosis (fALS). Consistent with the hypothesis that deposition of protein aggregates in neurodegenerative disorders reflects upstream dysfunction, we demonstrated that SOD1 in the Parkinson’s disease brain exhibits evidence of misfolding and metal deficiency, similar to that seen in mutant SOD1 in fALS. Our data suggest common mechanisms of toxic SOD1 aggregation in both disorders and a potential role for SOD1 dysfunction in neuronal loss in the Parkinson’s disease brain. This shared restricted proteinopathy highlights the potential translation of therapeutic approaches targeting SOD1 toxicity, already in clinical trials for ALS, into disease-modifying treatments for Parkinson’s disease.
“Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson’s disease brain” by Benjamin G. Trist, Katherine M. Davies, Veronica Cottam, Sian Genoud, Richard Ortega, Stéphane Roudeau, Asuncion Carmona, Kasun De Silva, Valerie Wasinger, Simon J. G. Lewis, Perminder Sachdev, Bradley Smith, Claire Troakes, Caroline Vance, Christopher Shaw, Safa Al-Sarraj, Helen J. Ball, Glenda M. Halliday, Dominic J. Hare, and Kay L. Double in Acta Neuropathologica. Published online May 17 2017 doi:10.1007/s00401-017-1726-6
http://neurosciencenews.com/sod1-als-parkinsons-6744/
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