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Aldehyde dehydrogenases (ALDH) play a key role in neuronal protection. They exert this function by metabolizing biogenic amine-related aldehydes, e.g. 3,4-dihydroxyphenylacetaldehyde (DOPAL), and by protecting neurons against aldehyde- and oxidative stress-related neurotoxicity. The role of these different isoenzymes has been discussed in other neurodegenerative disorders before. It is somewhat surprising that only few studies have investigated their role in the aetiology of Parkinson's disease (PD), in both the degeneration of dopaminergic neurons and the formation of Lewy bodies. Earlier studies report severe alterations of the cytosolic isoform of ALDH expression (ALDH 1A1) in the substantia nigra of patients with PD. However, there are no data regarding the activity of ALDH 2 located at the inner mitochondrial membrane. Since mitochondrial dysfunctions are hypothesized to be of importance in the aetiology of PD we have examined the enzymatic activity of mitochondrial ALDH 2 in post-mortem putamen and frontal cortex of patients with PD and controls. We found that mitochondrial ALDH 2 activity in contrast to the frontal cortex was significantly increased in the putamen of patients with PD compared to controls., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We report a meta-analysis of the brain neurochemical abnormalities in Alzheimer's (AD) and Parkinson's disease (PD). Evidence for oxidative stress, and disorders of energy metabolism and excitatory amino acids is presented for both disorders. However, limited data and conflicting findings preclude any definitive statement relating to differences and overlap between the two conditions.

A group of twelve patients with idiopathic Parkinson's disease was assessed both on and off L-Dopa medication on a range of tests of cognitive performance. Withdrawal of L-Dopa produced impairments in tests sensitive to frontal lobe dysfunction such as verbal fluency and the Tower of London task. Another test of frontal lobe function, the Wisconsin Card Sorting Test, was not affected in the absence of L-Dopa. Memory functions such as short-term span and verbal paired associate memory were not impaired by L-Dopa withdrawal. The results suggest that some of the cognitive impairments observed in Parkinson's disease, namely frontal lobe deficits, are related to a loss of central dopaminergic function.

Patients with idiopathic Parkinson's disease and control subjects were given two types of time estimation task. In the verbal estimation task subjects were required to judge the duration of time intervals of 10, 30 and 60 seconds, signalled by the examiner. Operative estimation required subjects to indicate when intervals of 10, 30 and 60 seconds had passed. Parkinsonian patients off L-Dopa medication were less accurate than control subjects in both tasks. They underestimated the time intervals determined by the examiner in the verbal estimation task, while in the operative estimation task parkinsonian subjects overestimated the required time intervals compared with controls. The administration of L-Dopa to the parkinsonian patients led to time judgements that were similar to those of control subjects. The present findings lend support to the hypothesis of the role of dopamine in the modulation of the internal clock.

Research on Parkinson's disease has led to new hypotheses concerning the mechanisms of neurodegeneration and to the development of neuroprotective agents. Recent findings of impaired mitochondrial function, altered iron metabolism and increased lipid peroxidation in the substantia nigra of parkinsonian patients emphasize the significance of oxidative stress and free radical formation in the pathogenesis of Parkinson's disease. Present research is therefore focussing on improvements in neuroprotective therapy to prevent or slow the rate of progression of the disease. Possible neuroprotective strategies include free radical scavengers, monoamine oxidase-B inhibitors, iron chelators and glutamate antagonists. Recent studies point to the possibility of achieving neuroprotection in ageing and parkinsonism by the administration of dopamine agonists. In the rat, the dopamine agonist pergolide appears to preserve the integrity of nigrostriatal neurones with ageing. The prevention of age-related degeneration may be achieved as a result of a decreased dopamine turnover and reduced conversion of dopamine to toxic compounds. In our own study, bromocriptine treatment prevented the striatal dopamine reduction following MPTP administration in the mouse. These results suggest that the neurotoxic effects of MPTP can be prevented by bromocriptine. Monotherapy with the dopamine agonist lisuride in the early stages of Parkinson's disease delays the need for the initiation of levodopa treatment to a similar extent as has been reported for L-deprenyl. It remains to be shown whether this is due to neuroprotective efficacy of the dopamine agonist or to a direct symptomatic effect.

High performance liquid chromatography with electrochemical detection was used for determining dopamine sulfate in human brain tissues. Dopamine sulfate was examined in the striatum and frontal cortex of human brain. The concentrations of dopamine sulfate in these regions are extremely low in comparison to free dopamine, and to dopamine sulfoconjugates in the cerebrospinal fluid, plasma and urine. Data obtained with this technique in human post mortem brain specimens indicate that the analysis of tissues and body fluids for dopamine conjugates is useful for profiling metabolic dopamine activity in controls and neurodegenerative disorders like Parkinson's disease.

In four human controls, four cases of Parkinson's disease and three cases of amyotrophic lateral sclerosis analysis of dopamine, noradrenaline, serotonin and the metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid was performed in various segments of postmortem spinal cord. In controls the concentrations of dopamine are about 1/3 to 1/4 that of noradrenaline; the significantly highest content of noradrenaline was found in the lumbar, and dopamine in thoracic, lumbar and sacral segments of the spinal cord. Intersegmental distribution of monoamines was only present in spinal cord of controls, while in the spinal cord of parkinsonian patients such a difference was not found. Otherwise, biogenic amine and metabolite concentrations in spinal cord segments of parkinsonian patients did not differ significantly from those in the control subjects. However, it cannot be excluded that these segments are sensitive to drugs including neuroleptics and combined L-DOPA treatment. In subjects with amyotrophic lateral sclerosis significantly lower concentrations of noradrenaline in the cervical and thoracic, and of dopamine and homovanillic acid in the thoracic and lumbar segments were found in comparison with controls. The concentrations of serotonin and 5-hydroxyindoleacetic acid in the thoracic segments of amyotrophic lateral sclerosis were significantly lower than that of controls. Differences in the inter-segmental distribution of noradrenaline in lumbar, lumbar-sacral, and serotonin in lumbar segments of spinal cord were found in this group.