Translational Neurodegeneration, a platform to share knowledge and experience in translational study of neurodegenerative diseases

Indeed, the prevalence of neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), has increased significantly as global populations age. Specifically, the number of cases of dementia in the developed world is projected to rise from 13.5 million in 2000 to 21.2 million in 2025, and to 36.7 million in 2050[1]. Currently, the number of deaths caused by AD is only next to the number of deaths caused by stroke. As the prevalence of AD grows, so does the cost to a nation. For PD, the second most common neurodegenerative disease after AD, more than 4 million people suffer from this devastating disease worldwide and that will double in the next 25 years [2]. To date, PD is still an incurable progressive neurological disorder that seriously impairs the quality of life.The discovery and application of levodopa (L-dopa) is one of the best examples of translational research for neurodegenerative diseases. In 1910s, L-dopa was first isolated from seedlings of Vicia faba; and in 1938, L-dopa decarboxylase was discovered, which can produce dopamine (DA) from L-dopa. In 1959, DA was found enriched in the basal ganglia; and in 1960, a severe striatal DA deficit was demonstrated in PD patients. These major discoveries and a deepening understanding of the neurochemistry of DA and the neuropathology of PD led to the concept of "DA replacement" with L-dopa. In 1961, L-dopa was tried in PD patients by i.v. treatment. In 1967, oral administration of L-dopa was reported to produce dramatic improvements in PD patients with increasing amounts over long periods [3]. However, the main side effects of increasing L-dopa administration, i.e., dyskinesias and motor fluctuations, became apparent. This clinical finding confused doctors and patients, and a solution was needed. In 1970s, the key cause was found. L-dopa decarboxylase degraded L-dopa to DA in peripheral blood, which can not across the blood-brain barrier. These findings led to the first L-dopa combi