Journal of Neural Transmission, Supplement 71
Supplement 71 to Journal of Neural Transmission contains articles, edited by Prof. H. Parvez (Institute Alfred Fessard de Neurosciences, France) and Prof. P. Riederer (Klinik und Poliklinik fur Psychiatrie und Psychotherapie, Germany). They deal with oxidative stress and neuroprotection in neurodegenerative diseases.
Parkinsonís disease therapy is based on levodopa, being the most widespread and effective drug. It is a gold standard, with which other methods of treatment, including surgical ones, are compared. A response to levodopa treatment is one of the clinical and diagnostic criteria of Parkinsonís disease. The main factor, limiting its use, is development of motor disorders, i.e. the so-called dyskinesias. L-DOPA was studied with the purpose of estimating its ability to promote parkinsonism progression. According to the results of this double blind randomized study, parkinsonism manifestations were less frequent in patients, who had taken levodopa during 40 weeks, as compared to placebo cases. The same effect was watched after taking this drug for a longer period of time. Thus, one can conclude, that levodopa slows down disease progression.
Use of pramipexole instead of dopamine agonists was caused by the achieved antispasmodic and antidepressive effect.
Treatment of dementia with donepezil in parkinsonian cases was effective only in patients with no therapy termination due to development of side effects (nausea, vomiting, dizziness).
Pathophysiology and strategy of treatment of psychosis, developing in Parkinsonís disease, were studied.
Antioxidant capacity of different segments of postmortem brain tissue was estimated in cases with Parkinsonís and Alzheimerís disease. Impairment of the capacity to neutralize free radicals was demonstrated.
The supplement contains information on molecular mechanisms of neurodegeneration and neuroprotection. A new function of MAO A in induction and regulation of apoptosis is described. A possible mechanism of neuroprotection of MAO B inhibitors may be related not only to MAO B suppression, but also to induction and activation of multiple factors for antioxidant stress and anti-apoptosis (catalase, superoxide dismutase 1 and 2, thioredoxin, etc.). The obtained data can become a basis of new strategy of rendering care in neurodegenerative disorders. For example, isatin, an endogeneous MAO inhibitor, considerably improved motor function in a developed rat model of Parkinsonís disease and strengthened a neuroprotective effect of deprynil.
Thousands of clinicians and basic neuroscience researchers are involved in search for neuroprotective therapy of parkinsonism. Their joint efforts allow to find new approaches to neuroprotective therapy. It has been shown, that besides MAO inhibitors (deprynil, rasagiline) an evident neuroprotective effect is inherent in dopaminergic agonists (ropinirole, pramixepole) and levodopa. Neuroprotective properties of glutamate antagonists, inhibitors of microglial activation, neurotrophin-like compounds are being investigated. Identification of markers for a preclinical diagnosis of Parkinsonís disease is of extreme importance for neuroprotection. PET and SPECT can be used for determination of risk factors before appearance of motor disorders. Changes in the substantia nigra, revealed by PET and SPECT, and their combination with minor motor disturbances can serve the basis for including individuals under study into a group with a risk of Parkinsonís disease development.
Today a great attention is paid to iron deficiency and its role in parkinsonism development. Treatment, based on regulation of iron content in dopaminergic neurons, can reduce neurodegeneration in Parkinsonís disease.
Summarizing the aforesaid, one should emphasize, that the present supplement to Journal of Neural Transmission contains detailed information on urgent problems of parkinsonism treatment. It is interesting both for doctors, studying neurology or practicing in this field, as well as neurosurgeons and can be recommended for use during training these specialists.