Environmental Toxins and Parkinson's Disease (original) (raw)
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The role of free radicals in the aging brain and Parkinson's disease: Convergence and parallelism
2012
Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson's disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5-10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3β, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD.
Aging of the Nigrostriatal Pathway in Humans
Canadian Journal of Neurological Sciences, 1987
Progressive degeneration of functionally related groups of neurons occurs in certain infective, toxic, nutritional and genetically determined neurological diseases. It also takes place in normal aging, and several of the regions that undergo selective decay with the passage of time seem to be the same target regions that are afflicted in degenerative disorders such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS). Infective etiology is relatively easy to exclude by a combination of immunological tests and transfer experiments. Genetic causation can be rendered unlikely when large kindreds are available for study. Nutritional deprivation and acute or subacute toxicity are accessible to explanation by examining the environment. The most difficult mechanism of pathogenesis to refute is chronic toxic damage, where the lesion may derive from long-term exposure to a relatively widespread noxious agent or agents. Variations in involvement of individuals within a population may stem from differing capacities to activate or inactivate a toxin. Inherent in this concept of etiology is recognition that compensatory potential within the central nervous system may contribute to prolonged existence of subclinical lesions so that a latent period may exist for several decades, between causal event and the onset of symptoms. Furthermore, progressive clinical deterioration may take place even though the cause may have been transient, many years before. The histological features associated with Parkinson's disease, Alzheimer's disease and ALS may be nonspecific indicators of neuronal "illness", there being a predilection for certain morphological markers to appear more frequently in particular circumstances and particular regions associated with the pathology of particular diseases.
Parkinson's disease as a result of aging
Aging Cell, 2015
It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field.
Clinics in Geriatric Medicine, 2004
Aging, defined as the gradual alteration in structure and function that occurs over time, eventually leads to increased probability of nondisease-or nontrauma-related death [1]. Aging is associated with the impairment of physiological systems such as the central nervous system (CNS), homeostatic system, immune system, and others. Functional impairments of the CNS is associated with increased susceptibility to develop many neurodegenerative diseases such as Alzheimer's diseases (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Several theories have been offered to understand the phenomenon of aging through: (1) explaining how the loss of homeostasis occurs in individual organisms during the latter part of life, (2) accounting for the lifespan variation among cohort genetic strains and species, (3) identifying the crucial factors responsible for lifespan extension by genetic mutation or experimental regimens such as caloric restriction (CR), and (4) demonstrating that variation of senescent factors can manipulate the rate of aging [2]. A credible theory of aging should address these criteria. In the past 3 decades, Harman's free radical theory [3] has gained relatively strong support in this area. The free radical theory of aging postulates that the free radical reactions with biomolecules, such as proteins and lipid membranes, are responsible for the
Toxicology, 2016
As life expectancy increases worldwide, the time available for extended exposures to toxic materials present in the environment is increased. By this means the continuous presence of low levels of xenobiotic agents can exert a subtle effect on the aging process. The interaction of neurotoxic chemicals with the normal aging process is difficult to detect, as it can be very slow and progressive. Epidemiological investigation can be an important tool but since it is performed over a prolonged period, is subject to a large range of extraneous confounders. Animal experimentation is also useful but models of human aging are incomplete and extended low level dosing is expensive to carry out as well as also being subject to irrelevant factors. These difficulties should not negate the growing importance of this area of study. This review is intended to document some agents that may synergize with normal senescence and bring about a premature decline in optimal health. Many neurological diseases are found only with maturation or aging. Multiple sclerosis (MS), Huntingdon's disease (HD), amyotrophic lateral sclerosis (ALS) are associated with a relatively early stage of maturation while Alzheimer's disease (AD), Parkinson's disease (PD) generally occur at a later stage of aging. All of these disorders however, have in common that they are not found in childhood or in very young adults. The implication of this is that certain types of insufficiency can only be expressed in conjunction with a maturation/aging process. Thus aging plays a key role in enabling the emergence of these disorders. Once the aging process is under way it can permit the overt appearance of disease, which was previously only present in an occult form. Aging and maturation are thus essential platforms for the emergence of specific neurological diseases. Some of these disorders have a clear genetic origin. For example HD is a genetic disorder, which has a 100% penetrance. Others have a marked genetic component but studies on identical twins indicate incomplete penetrance, e.g., familial AD and PD. However the great majority of cases of neurodegenerative disorders are of idiopathic causation. This suggests that they are likely to be initiated or promoted by exogenous environmental factors. In addition, it is likely that the velocity of normal aging can be modulated in the presence of various environmental xenobiotic chemicals. 1.1 Parkinson's disease Idiopathic Parkinson's disease (PD) is a relatively common disorder of unknown cause, involving progressive loss of dopaminergic neurons ultimately leading to severe movement and postural deficits. There is no known cure for slowing the advancement of the disease. Although there are changes in several brain regions, the major symptoms of PD are attributable to the death of dopaminergic neurons in the substantia nigra and striatal structures. Due to their content of dopamine whose ready oxidation takes place by way of reactive oxidant intermediates, dopaminergic neurons are specifically susceptible to oxidative damage. Dopamine neurons are continually lost throughout the normal lifespan. Perhaps to compensate for their fragility, such neurons are present in striatal tissues in excess so that abnormalities in their circuitry with resulting behavioral inadequacies are not apparent until around 80% of neurons have been lost.
Ageing, Neurodegeneration and Parkinson's Disease
International Journal of Scientific Research in Science and Technology, 2022
For the human development aging is one of the important aspect among which on cellular processes and functions are predispose to neurodegeneration and synthetic changes in the body are involved in the pathogenesis of Parkinson’s. The accumulation of the cellular development and their function leads to the progression of Parkinson’s. The formation of ROS, generation of oxidative stress, disruptions in inflammatory pathways like COX, LOX, formation of lewy bodies, protein degradation, genetic mutations, mitochondrial depletion and several other pathways involved in the pathogenies. These may be due to age related decline in acetylcholine and dopamine levels. On medical findings from survey it's been discovered Parkinson’s is age associated ailment and quite a times irreversible yet curable on early stages and can be treated with dopamine and acetylcholine analogues, where levodopa and carbidopa is considered to be the drug of choice at different doses for the inhibiting progression of Parkinson’s.
Oxidative damage and cerebral aging
Progress in Neurobiology, 1992
CONTENTS 1. Introduction 2. The free radical theory of cerebral aging 3. General properties of reactive oxygen species and their measurement 601 601 602 602 603 603 604 605 606 606 606 4. Factors underlying cerebral reactive oxygen species formation 5. Factors associated with excess formation of cerebral reactive oxygen species 6. Mitigation of cerebral oxidative stress 7. Age-related alterations in the brain associated with reactive oxygen species 8. Proposed alternatives to the free radical theory of aging 9. Physiological exploitation of free radicals 10. A consolidated theory of cerebral oxidative stress and aging References