A New Hypothesis of the Etiology of Amyotrophic Lateral Sclerosis

Bradley, Walter G.; Krasin, Frank

doi:10.1001/archneur.1982.00510230003001

Cited by 91 publications

(30 citation statements)

References 24 publications

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“…Increased DNA lesions have also been detected in the brains of PD patients compared with age-matched controls (78). DNA damage can also be involved in the pathogenesis of ALS (57,72). DNA damage in ALS may be caused by oxidative stress from mitochondrial or superoxide dismutase 1 dysfunction (23), and OHdG adducts are elevated in postmortem CNS tissue extracts from individuals with ALS (79).…”

Section: Elevated Dna Damage Is Found In Several Neurodegenerative DImentioning

confidence: 99%

DNA Damage and Repair

Martin

2008

J Neuropathol Exp Neurol

175

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DNA damage is a form of cell stress and injury that has been implicated in the pathogenesis of many neurologic disorders, including amyotrophic lateral sclerosis, Alzheimer disease, Down syndrome, Parkinson disease, cerebral ischemia, and head trauma. However, most data reveal only associations, and the role for DNA damage in direct mechanisms of neurodegeneration is vague with respect to being a definitive upstream cause of neuron cell death, rather than a consequence of the degeneration. Although neurons seem inclined to develop DNA damage during oxidative stress, most of the existing work on DNA damage and repair mechanisms has been done in the context of cancer biology using cycling nonneuronal cells but not nondividing (i.e. postmitotic) neurons. Nevertheless, the identification of mutations in genes that encode proteins that function in DNA repair and DNA damage response in human hereditary DNA repair deficiency syndromes and ataxic disorders is establishing a mechanistic precedent that clearly links DNA damage and DNA repair abnormalities with progressive neurodegeneration. This review summarizes DNA damage and repair mechanisms and their potential relevance to the evolution of degeneration in postmitotic neurons.

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Section: Elevated Dna Damage Is Found In Several Neurodegenerative DImentioning

confidence: 99%

DNA Damage and Repair

Martin

2008

J Neuropathol Exp Neurol

175

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“…No relationship has been found between MND and viral infections [2], HLA types [3], or cancer [4], Heavy metals and calcium [5,6] may provoke MND, but other factors suggested are ageing [7], ante cedent mechanical injuries [8] and heavy manual labor [9][10][11]. Another recently advanced hypothesis suggests that the primary abnormality in MND is a deficiency of one of the DNA-repairing enzymes [12].…”

Section: Introductionmentioning

confidence: 99%

Motor Neuron Disease and Heavy Manual Labor: An Epidemiologic Survey of Värmland County, Sweden

Gunnarsson¹,

Palm²

1984

Neuroepidemiology

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89 cases of motor neuron disease (MND) were identified in Värmland County during the period 1970–1981. This amounts to an annual incidence rate of 2.6 per 100,000 population, sex- and age-adjusted to the USA population, 1.7. The average point prevalence was 8.5 per 100,000 population and the median duration of MND was 25 months. 95% of the MND cases in Värmland County were coded MND on their death certificates. MND was overrepresentated in persons performing heavy manual labor. A significantly higher mortality rate of MND in Värmland County was found compared to all Sweden (p < 0.01). One explanation for this can be that more people in this county perform heavy manual labor.

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“…The etiology of the disease is not known and treatment is not available. Among the proposed but not proven hypotheses concerning the etiology of the disease are the following: a lesion of skeletal muscle and/or end plate causing a retrograde atrophy of motor neurons, autoimmunity, viral infection, failure of a putative growth or maintenance factor, toxic agents, and aging (2)(3)(4)(5)(6)(7).…”

mentioning

confidence: 99%