Lancet neurology
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Review
Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson's disease.
Clinical use of allografts of fetal ventral mesencephalic tissue as a treatment to replace dopaminergic neurons in patients with Parkinson's disease was first done more than 20 years ago. Since then, many patients have received transplants, with variable results. During this time, our knowledge of Parkinson's disease has changed and the nature and extent of problems associated with the disorder have been better defined. Our understanding on how best to implement this cell-replacement strategy for patients has grown, but gaining this insight has entailed critical reappraisal of data from transplant trials that have already been undertaken.
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Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. ⋯ In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible.