Antioxidants as treatment for neurodegenerative disorders
- 1 October 2002
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 11 (10), 1407-1435
- https://doi.org/10.1517/13543784.11.10.1407
Abstract
Oxidative stress is a ubiquitously observed hallmark of neurodegenerative disorders. Neuronal cell dysfunction and cell death due to oxidative stress may causally contribute to the pathogenesis of progressive neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, as well as acute syndromes of neurodegeneration, such as ischaemic and haemorrhagic stroke. Neuroprotective antioxidants are considered a promising approach to slowing the progression and limiting the extent of neuronal cell loss in these disorders. The clinical evidence demonstrating that antioxidant compounds can act as protective drugs in neurodegenerative disease, however, is still relatively scarce. In the following review, the available data from clinical, animal and cell biological studies regarding the role of antioxidant neuroprotection in progressive neurodegenerative disease will be summarised, focussing particularly on Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. The general complications in developing potent neuroprotective antioxidant drugs directed against these long-term degenerative conditions will also be discussed. The major challenges for drug development are the slow kinetics of disease progression, the unsolved mechanistic questions concerning the final causalities of cell death, the necessity to attain an effective permeation of the blood–brain barrier and the need to reduce the high concentrations currently required to evoke protective effects in cellular and animal model systems. Finally, an outlook as to which direction antioxidant drug development and clinical practice may be leading to in the near future will be provided.Keywords
This publication has 100 references indexed in Scilit:
- An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer's diseaseJournal of Neural Transmission, 2000
- Altered redox state of platelet coenzyme Q 10 in Parkinson's diseaseJournal of Neural Transmission, 2000
- Compounds that Induce Isoforms of Glutathione S-transferase with Properties of a Critical Enzyme in Defense against Oxidative StressBiochemical and Biophysical Research Communications, 1999
- Novel Free Radical Spin Traps Protect against Malonate and MPTP NeurotoxicityExperimental Neurology, 1999
- Recent Trends in Glutathione Biochemistry—Glutathione–Protein Interactions: A Molecular Link between Oxidative Stress and Cell Proliferation?Biochemical and Biophysical Research Communications, 1998
- Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in manJournal of Neural Transmission, 1996
- Nigrostriatal function in vitamin E deficiency: Clinical, experimental, and positron emission tomographic studiesAnnals of Neurology, 1994
- The determination of hydroxydopamines and other trace amines in the urine of Parkinsonian patients and normal controlsNeurochemical Research, 1993
- Vitamin E protects nerve cells from amyloid βprotein toxicityBiochemical and Biophysical Research Communications, 1992
- Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid proteinBiochemical and Biophysical Research Communications, 1984