Novel mechanism to a rare neurodegenerative disease

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, result from the accumulation of protein aggregates in cells. Despite extensive research, many of these diseases remain poorly understood, and it is likely that some have yet to be discovered. A recent study identified a mutation in the regulatory subunit of Protein Kinase A (PKA), specifically RIβ-L50R, in individuals with a rare neurodegenerative disease characterized by dementia and/or parkinsonism. In a study published in Brain, Dr. Ronit Ilouz and associates elucidated the molecular mechanism underlying this disease. They developed a mouse model carrying the RIβ-L50R mutation to mimic the human condition. Protein aggregates were observed in the brains of these mice at an early age,  although symptoms, such as impaired motor performance, emerged later. Intriguingly, the researchers found that RIβ-L50R aggregation could be reversed through the binding of another PKA subunit, known as the C-subunit, offering a potential therapeutic avenue.