Structural insights into human angiogenin variants implicated in Parkinson's disease and Amyotrophic Lateral Sclerosis

William J. Bradshaw, Saima Rehman, Tram T. K. Pham, Nethaji Thiyagarajan, Rebecca L. Lee, Vasanta Subramanian, K. Ravi Acharya

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Abstract

Mutations in Angiogenin (ANG), a member of the Ribonuclease A superfamily (also known as RNase 5) are known to be associated with Amyotrophic Lateral Sclerosis (ALS, motor neurone disease) (sporadic and familial) and Parkinson's Disease (PD). In our previous studies we have shown that ANG is expressed in neurons during neuro-ectodermal differentiation, and that it has both neurotrophic and neuroprotective functions. In addition, in an extensive study on selective ANG-ALS variants we correlated the structural changes to the effects on neuronal survival and the ability to induce stress granules in neuronal cell lines. Furthermore, we have established that ANG-ALS variants which affect the structure of the catalytic site and either decrease or increase the RNase activity affect neuronal survival. Neuronal cell lines expressing the ANG-ALS variants also lack the ability to form stress granules. Here, we report a detailed experimental structural study on eleven new ANG-PD/ALS variants which will have implications in understanding the molecular basis underlying their role in PD and ALS.

LanguageEnglish
Article number41996
JournalScientific Reports
Volume7
DOIs
StatusPublished - 8 Feb 2017

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Amyotrophic Lateral Sclerosis
Parkinson Disease
Cell Line
Pancreatic Ribonuclease
Ribonucleases
angiogenin
Catalytic Domain
Neurons
Mutation

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Structural insights into human angiogenin variants implicated in Parkinson's disease and Amyotrophic Lateral Sclerosis. / Bradshaw, William J.; Rehman, Saima; Pham, Tram T. K.; Thiyagarajan, Nethaji; Lee, Rebecca L.; Subramanian, Vasanta; Acharya, K. Ravi.

In: Scientific Reports, Vol. 7, 41996, 08.02.2017.

Research output: Contribution to journalArticle

Bradshaw, William J. ; Rehman, Saima ; Pham, Tram T. K. ; Thiyagarajan, Nethaji ; Lee, Rebecca L. ; Subramanian, Vasanta ; Acharya, K. Ravi. / Structural insights into human angiogenin variants implicated in Parkinson's disease and Amyotrophic Lateral Sclerosis. In: Scientific Reports. 2017 ; Vol. 7.
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