Copper Homeostasis and Neurodegenerative Disorders (Alzheimer's, Prion, and Parkinson's Diseases and Amyotrophic Lateral Sclerosis)

2006 ◽  
Vol 106 (6) ◽  
pp. 1995-2044 ◽  
Author(s):  
Elena Gaggelli ◽  
Henryk Kozlowski ◽  
Daniela Valensin ◽  
Gianni Valensin
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disorders ◽  
Copper Homeostasis ◽  
Parkinson’S Diseases ◽  
Lateral Sclerosis

scholarly journals The Diagnostic Potential of Amyloidogenic Proteins

2021 ◽  
Vol 22 (8) ◽  
pp. 4128
Author(s):  
Yiyun Jin ◽  
Devkee Mahesh Vadukul ◽  
Dimitra Gialama ◽  
Ying Ge ◽  
Rebecca Thrush ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Neurodegenerative Disorders ◽  
Early Treatment ◽  
Future Developments ◽  
Amyloidogenic Proteins ◽  
Diagnostic Potential ◽  
Parkinson’S Diseases ◽  
Specific Proteins ◽  
Lateral Sclerosis

Neurodegenerative disorders are a highly prevalent class of diseases, whose pathological mechanisms start before the appearance of any clear symptoms. This fact has prompted scientists to search for biomarkers that could aid early treatment. These currently incurable pathologies share the presence of aberrant aggregates called amyloids in the nervous system, which are composed of specific proteins. In this review, we discuss how these proteins, their conformations and modifications could be exploited as biomarkers for diagnostic purposes. We focus on proteins that are associated with the most prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, and frontotemporal dementia. We also describe current challenges in detection, the most recent techniques with diagnostic potentials and possible future developments in diagnosis.

scholarly journals Nucleolin Rescues TDP-43 Toxicity in Yeast and Human Cell Models

2021 ◽  
Vol 15 ◽  
Author(s):  
Caterina Peggion ◽  
Maria Lina Massimino ◽  
Roberto Stella ◽  
Raissa Bortolotto ◽  
Jessica Agostini ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cell Viability ◽  
Human Cell ◽  
Neurodegenerative Disorders ◽  
Nuclear Protein ◽  
Human Cells ◽  
Cell Models ◽  
Nuclear Retention ◽  
Beneficial Effects ◽  
Lateral Sclerosis

TDP-43 is a nuclear protein involved in pivotal processes, extensively studied for its implication in neurodegenerative disorders. TDP-43 cytosolic inclusions are a common neuropathologic hallmark in amyotrophic lateral sclerosis (ALS) and related diseases, and it is now established that TDP-43 misfolding and aggregation play a key role in their etiopathology. TDP-43 neurotoxic mechanisms are not yet clarified, but the identification of proteins able to modulate TDP-43-mediated damage may be promising therapeutic targets for TDP-43 proteinopathies. Here we show by the use of refined yeast models that the nucleolar protein nucleolin (NCL) acts as a potent suppressor of TDP-43 toxicity, restoring cell viability. We provide evidence that NCL co-expression is able to alleviate TDP-43-induced damage also in human cells, further supporting its beneficial effects in a more consistent pathophysiological context. Presented data suggest that NCL could promote TDP-43 nuclear retention, reducing the formation of toxic cytosolic TDP-43 inclusions.

scholarly journals Inherited and Sporadic Amyotrophic Lateral Sclerosis and Fronto-Temporal Lobar Degenerations arising from Pathological Condensates of Phase Separating Proteins

2019 ◽  
Vol 28 (R2) ◽  
pp. R187-R196 ◽  
Author(s):  
Michael Fernandopulle ◽  
GuoZhen Wang ◽  
Jonathon Nixon-Abell ◽  
Seema Qamar ◽  
Varun Balaji ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Recent Work ◽  
Neurodegenerative Disorders ◽  
Low Complexity ◽  
Present Review ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Missense Mutations ◽  
Post Translational Modifications ◽  
Intrinsically Disordered ◽  
Lateral Sclerosis

Abstract Recent work on the biophysics of proteins with low complexity, intrinsically disordered domains that have the capacity to form biological condensates has profoundly altered the concepts about the pathogenesis of inherited and sporadic neurodegenerative disorders associated with pathological accumulation of these proteins. In the present review, we use the FUS, TDP-43 and A11 proteins as examples to illustrate how missense mutations and aberrant post-translational modifications of these proteins cause amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD).

scholarly journals Non–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond

2009 ◽  
Vol 187 (6) ◽  
pp. 761-772 ◽  
Author(s):  
Hristelina Ilieva ◽  
Magdalini Polymenidou ◽  
Don W. Cleveland
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disorders ◽  
Cell Types ◽  
Neuronal Dysfunction ◽  
Inherited Disease ◽  
Supporting Cells ◽  
Cerebellar Ataxias ◽  
Multiple Cell ◽  
Lateral Sclerosis ◽  
Human Neurodegenerative Disease

Selective degeneration and death of one or more classes of neurons is the defining feature of human neurodegenerative disease. Although traditionally viewed as diseases mainly affecting the most vulnerable neurons, in most instances of inherited disease the causative genes are widely—usually ubiquitously—expressed. Focusing on amyotrophic lateral sclerosis (ALS), especially disease caused by dominant mutations in Cu/Zn superoxide dismutase (SOD1), we review here the evidence that it is the convergence of damage developed within multiple cell types, including within neighboring nonneuronal supporting cells, which is crucial to neuronal dysfunction. Damage to a specific set of key partner cells as well as to vulnerable neurons may account for the selective susceptibility of neuronal subtypes in many human neurodegenerative diseases, including Huntington's disease (HD), Parkinson's disease (PD), prion disease, the spinal cerebellar ataxias (SCAs), and Alzheimer's disease (AD).

scholarly journals Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis

2017 ◽  
Vol 19 ◽  
Author(s):  
Francisco J Gil-Bea ◽  
Garazi Aldanondo ◽  
Haizpea Lasa-Fernández ◽  
Adolfo López de Munain ◽  
Ainara Vallejo-Illarramendi
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Prion Diseases ◽  
Disease Onset ◽  
Copper Homeostasis ◽  
The Central Nervous System ◽  
Novel Approaches ◽  
Copper Dyshomeostasis ◽  
Copper Delivery ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a severe neuromuscular disease characterised by a progressive loss of motor neurons that usually results in paralysis and death within 2 to 5 years after disease onset. The pathophysiological mechanisms involved in ALS remain largely unknown and to date there is no effective treatment for this disease. Here, we review clinical and experimental evidence suggesting that dysregulation of copper homeostasis in the central nervous system is a crucial underlying event in motor neuron degeneration and ALS pathophysiology. We also review and discuss novel approaches seeking to target copper delivery to treat ALS. These novel approaches may be clinically relevant not only for ALS but also for other neurological disorders with abnormal copper homeostasis, such as Parkinson's, Huntington's and Prion diseases.

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