scholarly journals Dysregulation of Iron Metabolism in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Satoru Oshiro ◽  
Masaki S. Morioka ◽  
Masataka Kikuchi
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Lateral Sclerosis

Dysregulation of iron metabolism has been observed in patients with neurodegenerative diseases (NDs). Utilization of several importers and exporters for iron transport in brain cells helps maintain iron homeostasis. Dysregulation of iron homeostasis leads to the production of neurotoxic substances and reactive oxygen species, resulting in iron-induced oxidative stress. In Alzheimer's disease (AD) and Parkinson's disease (PD), circumstantial evidence has shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation. Several genetic studies have revealed mutations in genes associated with increased iron uptake, increased oxidative stress, and an altered inflammatory response in amyotrophic lateral sclerosis (ALS). Here, we review the recent findings on brain iron metabolism in common NDs, such as AD, PD, and ALS. We also summarize the conventional and novel types of iron chelators, which can successfully decrease excess iron accumulation in brain lesions. For example, iron-chelating drugs have neuroprotective effects, preventing neural apoptosis, and activate cellular protective pathways against oxidative stress. Glial cells also protect neurons by secreting antioxidants and antiapoptotic substances. These new findings of experimental and clinical studies may provide a scientific foundation for advances in drug development for NDs.

scholarly journals Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Yui Nakayama ◽  
Satoru Morimoto ◽  
Misao Yoneda ◽  
Shigeki Kuzuhara ◽  
Yasumasa Kokubo
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Lateral Sclerosis

Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (), Alzheimer’s disease (), Parkinson’s disease (), amyotrophic lateral sclerosis (), and controls () using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson’s disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease.

scholarly journals Cellular Senescence and Iron Dyshomeostasis in Alzheimer’s Disease

2019 ◽  
Vol 12 (2) ◽  
pp. 93 ◽  
Author(s):  
Shashank Masaldan ◽  
Abdel Ali Belaidi ◽  
Scott Ayton ◽  
Ashley I. Bush
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydroxyl Radicals ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Dependent Cell ◽  
Cellular Dysfunction ◽  
The Impact ◽  
The Brain

Iron dyshomeostasis is a feature of Alzheimer’s disease (AD). The impact of iron on AD is attributed to its interactions with the central proteins of AD pathology (amyloid precursor protein and tau) and/or through the iron-mediated generation of prooxidant molecules (e.g., hydroxyl radicals). However, the source of iron accumulation in pathologically relevant regions of the brain and its contribution to AD remains unclear. One likely contributor to iron accumulation is the age-associated increase in tissue-resident senescent cells that drive inflammation and contribute to various pathologies associated with advanced age. Iron accumulation predisposes ageing tissue to oxidative stress that can lead to cellular dysfunction and to iron-dependent cell death modalities (e.g., ferroptosis). Further, elevated brain iron is associated with the progression of AD and cognitive decline. Elevated brain iron presents a feature of AD that may be modified pharmacologically to mitigate the effects of age/senescence-associated iron dyshomeostasis and improve disease outcome.

Amyotrophic Lateral Sclerosis, Parkinson’s Disease and Alzheimer’s Disease: Phylogenetic Disorders of the Human Neocortex Sharing Many Characteristics

1992 ◽  
Vol 19 (S1) ◽  
pp. 117-123 ◽  
Author(s):  
Andrew Eisen ◽  
Donald Calne
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Neuronal Degeneration ◽  
Early Morning ◽  
Hla Dr ◽  
By Products ◽  
Lateral Sclerosis

ABSTRACT:Features common to amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD) are reviewed. Shared epidemiological aspects include an increasing frequency which is proportional for each disease. We draw attention to geographic non-uniform distribution which, for ALS and PD, correlates positively with latitude. Clinical and pathological overlap occurs in the same patients, and in members of the same family. A high early morning plasma cysteine/sulphate ratio possibly related to the development of proteinacious inclusions, as well as ubiquinated neuronal inclusions, characterize ALS, PD and AD. HLA-DR (the human group II major histocompatibility class) staining is marked in ALS, PD and AD and may represent autoimmunity-incited by-products of neuronal degeneration. Based upon demonstrated glutaminergic connections between the neocortex and anterior horn cells, the entorhinal cortex and the basal ganglia we hypothesize that ALS, AD and PD are phylogenetic disturbances of the neocortical cell. The postsynaptic neuron may degenerate secondarily to anterograde effects of deranged glutamate metabolism. Future therapeutic strategies should be directed to agents that decrease transmission induced by excitatory amino-acids.

scholarly journals Eosinophil-Derived Neurotoxin Is Elevated in Patients with Amyotrophic Lateral Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Guan-Ting Liu ◽  
Chi-Shin Hwang ◽  
Chia-Hung Hsieh ◽  
Chih-Hao Lu ◽  
Sunny Li-Yun Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
High Mobility ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Lateral Sclerosis

Background and Objectives. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the brainstem, motor cortex, and spinal cord. Oxidative stress and neuroinflammation have been implicated in the pathophysiology of ALS. Members of the family of damage-associated molecular patterns, including reactive oxygen species, high-mobility group box 1, and eosinophil-derived neurotoxin (EDN), may participate in pathological conditions. In this study, we aim to discover new biomarker for detecting ALS.Materials and Methods. We examined 44 patients with ALS, 41 patients with Alzheimer’s disease, 41 patients with Parkinson’s disease, and 44 healthy controls. The concentration of serum EDN was measured using an enzyme-linked immunosorbent assay.Results. EDN levels were significantly increased 2.17-fold in the serum of patients with ALS as compared with healthy controls (P<0.05). No correlation between the levels of serum EDN and various clinical parameters of ALS was found. Moreover, the levels of serum EDN in patients with Parkinson’s disease and Alzheimer’s disease and healthy controls were similar.Conclusion. A higher level of serum EDN was found specifically in patients with ALS, indicating that EDN may participate in the pathophysiology of ALS.

Sign in / Sign up

Export Citation Format

Share Document