Journal article

Rilmenidine promotes MTOR-independent autophagy in the mutant SOD1 mouse model of amyotrophic lateral sclerosis without slowing disease progression

Nirma D Perera, Rebecca K Sheean, Chew L Lau, Yea Seul Shin, Philip M Beart, Malcolm K Horne, Bradley J Turner



Macroautophagy/autophagy is the main intracellular catabolic pathway in neurons that eliminates misfolded proteins, aggregates and damaged organelles associated with ageing and neurodegeneration. Autophagy is regulated by both MTOR-dependent and -independent pathways. There is increasing evidence that autophagy is compromised in neurodegenerative disorders, which may contribute to cytoplasmic sequestration of aggregation-prone and toxic proteins in neurons. Genetic or pharmacological modulation of autophagy to promote clearance of misfolded proteins may be a promising therapeutic avenue for these disorders. Here, we demonstrate robust autophagy induction in motor neuronal cells expressing SO..

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Awarded by Australian National Health and Medical Research Council

Funding Acknowledgements

This work was supported by grants from the Australian National Health and Medical Research Council (Project Grants 1104299 and 1104295), Stafford Fox Medical Research Foundation, MND Research Institute of Australia (Susie Harris Memorial Fund and Zo-ee MND Research Grants), Bethlehem Griffiths Research Foundation, Cavalier Courage MND Research Grant, Melbourne Support Grant Research Scheme and Inner Wheel Club of Pakenham. The Florey Institute of Neuroscience and Mental Health acknowledge the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. N.D.P. is supported by an Australian Postgraduate Award Scholarship.