The finding of SOD variants in FALS is consistent with the hypothesis that free radicals contribute to the pathogenesis of FALS, and possibly to the pathogenesis of other neurodegenerative disorders such as Parkinson's disease, in which there is substantial evidence of oxidant stress.
To evaluate the possibility of a shared genetic defect in amyotrophic lateral sclerosis and Parkinson's disease, the SOD1 gene was sequenced in index patients with familial Parkinson's disease from 23 families.No changes were detected.
Spinal cord from 11 ALS cases and 27 controls consisting of 15 cases of Alzheimer disease (AD), six cases of Parkinson disease (PD), three cases of cerebrovascular disease, and three control cases were analyzed.
Table 1 Biochemical Alterations in Substantia Nigra of Parkinson's Disease Indicating Oxidative Stress Elevated Decreased Iron (in microglia, astrocytes, oligodendrocytes, and melanized dopamine neurons and mitochondria) GSH (GSSG unchanged); GSH/GSSG ratio decreased Mitochondrial complex I Ferritin Calcium binding protein (calbindin 28) Mitochondrial monoamine oxidase B Transferrin and transferrin receptor Lipofuscin Vitamins E and C Ubiquitin Copper Cu/Zn-superoxide dismutase Cytotoxic cytokines (TNF-a, IL-1, IL-6) Inflammatory transcription factor NFKB Heme oxygenase-1 Ratio of oxidized to reduced glutathione (GSSG/GSH) Nitric oxide Neuromelanin.
Table 1 Biochemical Alterations in Substantia Nigra of Parkinson's Disease Indicating Oxidative Stress Elevated Decreased Iron (in microglia, astrocytes, oligodendrocytes, and melanized dopamine neurons and mitochondria) GSH (GSSG unchanged); GSH/GSSG ratio decreased Mitochondrial complex I Ferritin Calcium binding protein (calbindin 28) Mitochondrial monoamine oxidase B Transferrin and transferrin receptor Lipofuscin Vitamins E and C Ubiquitin Copper Cu/Zn-superoxide dismutase Cytotoxic cytokines (TNF-a, IL-1, IL-6) Inflammatory transcription factor NFKB Heme oxygenase-1 Ratio of oxidized to reduced glutathione (GSSG/GSH) Nitric oxide Neuromelanin.
We investigated the substantia nigra (SN) in MND cases; two cases of motor neurone disease inclusion body (MND-IB) dementia, six cases of DMND, 14 cases of MND (including one case from Guam and two cases of familial SOD1 mutation), four cases of Parkinson's disease (PD), and 10 cases of age-matched normal controls.
The loss of Cu,Zn-SOD m-RNA in SNc in MPTP-treated marmosets and patients with PD suggests that it is primarily located in dopaminergic neuronal cell bodies.
The followings, for instance, are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated Beta-amyloid peptide for Alzheimer's disease (AD), Alpha-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson's disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington's gene mutations in Huntington's disease (HD).
In the light of the possibility that different SOD1 entities could be expressed also in other neurodegenerative disorders, as a sort of unifying event with AD and PD, we have investigated amyotrophic lateral sclerosis (ALS) using human neuroblastoma SH-SY5Y cells with mutated SOD1 gene H46R as cellular model.
Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases.
Studies using invertebrate models expressing proteins associated with Huntington's disease, Alzheimer's disease, ALS, and Parkinson's disease have provided insights into the genetic networks and stress signaling pathways that regulate the proteostasis machinery to prevent cellular dysfunction, tissue pathology, and organismal failure.
Both ALS and PD are neurodegenerative diseases, and are characterized by the presence of intraneuronal inclusions; however, different classes of neurons are affected and the primary protein in the inclusions differs between the diseases, and in some cases is different in distinct forms of the same disease.
All the results indicated that KLF4 promoted the neurotoxicity of MPP + via inhibiting the transcription of SOD1, suggesting a potential mechanism of increased oxidative stress and cell death in Parkinson's disease.
Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss.
α-Synuclein plays a central role in the pathogenesis of PD whereas Cu, Zn superoxide dismutase (SOD1) is a key player in a subset of familial ALS cases.
Remarkably, disturbances of ALS signaling were shared between SCA2p and sporadic PD suggesting common molecular dysfunctions in PD and ALS including CACNA1, hnRNP, DDX and PABPC gene family perturbations.
Ataxin-2 (ATXN2) polyglutamine domain expansions of large size result in an autosomal dominantly inherited multi-system-atrophy of the nervous system named spinocerebellar ataxia type 2 (SCA2), while expansions of intermediate size act as polygenic risk factors for motor neuron disease (ALS and FTLD) and perhaps also for Levodopa-responsive Parkinson's disease (PD).
Laboratory and clinical studies on the potential role of CBD in Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia, were examined.