Success in Reversing Dementia in Mice Sets the Stage for Human Clinical Trials (IMAGE)
Caption
Neurodegenerative diseases such as Alzheimer's disease and dementia with Lewy body (DLB) are caused by the accumulation of aggregated amyloid beta and α-synucelin, respectively. The aggregated proteins impaired the proteasome activity, thereby exacerbating neuronal death. On the other hand, we developed a novel T-type calcium channel enhancer SAK3 in 2017. Since T-type calcium channel is critical for neurotransmitter release, SAK3 enhanced the acetylcholine release in the brain thereby improving learning and memory. We here found that calcium entry through T-type calcium channel activates protein kinase (CaMKII), thereby promoting Rpt-6 phosphorylation. The Rpt-6 phosphorylation promoted the degradation of aggregated amyloid beta and α-synucelin in neurons. This is the first disease modifying therapeutics in most neurodegenerative diseases such as Alzheimer's disease, dementia with Lewy body (DLB), Huntington disease (HD) and frontotemporal dementia (FTD).
Credit
Kohji Fukunaga
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Credit: Kohji Fukunaga
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