In addition, those pathological neurofilament accumulations are known in α-synuclein in Parkinson's disease (PD), Aβ and tau in Alzheimer's disease (AD), polyglutamine in CAG trinucleotide repeat disorders, superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP43), neuronal FUS proteins, optineurin (OPTN), ubiquilin 2 (UBQLN2), and dipeptide repeat protein (DRP) in amyotrophic lateral sclerosis (ALS).
Epidemiological data have linked cadmium exposure to neurotoxicity and to neurodegenerative diseases (e.g., Alzheimer's and Parkinson's disease), and to increased risk of developing ALS.
While among these iridoids, catalpol, 10-O-trans-p-coumaroylcatalpol, geniposide and harpagoside, in PD improved the expressions of GDNF and Bcl-2 proteins and TH-positive neurons by increasing the levels of antioxidant enzymes, SOD and GSH-P<sub>X</sub> and down-regulating insulin/IGF signalling via activation of MEK protein.
The misfolded SOD1 was also detected in CSF from a subset of Parkinson's disease and progressive supranuclear palsy, albeit with smaller amounts than those in sALS.
In two different transgenic (Tg) mouse models of adult-onset neurodegenerative disease, a human A53T-α-synuclein (hαSyn) model of Parkinson's disease (PD) and a human G93A-superoxide dismutase-1(hSOD1) model of amyotrophic lateral sclerosis (ALS), mortality and survivor morbidity were significantly greater than non-Tg mice and a Tg mouse model of Alzheimer's disease after neonatal traumatic brain injury (TBI).
Together, carrying allele G in the single nucleotide polymorphism (rs2070424 A/G) in SOD1, or allele C in the single nucleotide polymorphism (rs4880 T/C) in SOD2, enhances genetic susceptibility to Parkinson's disease.
The obtained data exhibited that inhibition of miR-137 or up-regulation of OXR1 ameliorated PD-induced oxidative stress injury, reduced pole-climbing time, but increased score for traction test as well as promoted viability and decreased apoptosis of neurons in PD model, accompanied with decreased MDA content and ROS levels, and increased SOD levels.
We propose that these non-genetic factors underlie the misfolding and dysfunction of SOD1 and other proteins in both PD and fALS, constituting a shared and tractable pathway to neurodegeneration.
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.
In particular, the principal isoform VDAC1 represents the main mitochondrial docking site of many misfolded proteins, such as amyloid β and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease and several SOD1 mutants in Amyotrophic Lateral Sclerosis.
This shared restricted proteinopathy highlights the potential translation of therapeutic approaches targeting SOD1 toxicity, already in clinical trials for ALS, into disease-modifying treatments for Parkinson's disease.
Most patients had not discussed a trial with their physician and only 21% had ever enrolled, with rates highest in ALS (36%), Parkinson's disease (36%) and MS (20%) and lowest among SLE (9%), MDD (11%) and Fibromyalgia (11%).
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).
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.
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.
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.
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.
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.
Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases.
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.