Iron-Induced Dopaminergic Cell Death In Vivo as a Model of Parkinson’s Disease

Gerlach, Manfred; Double, Kay L.; Riederer, Peter

doi:10.1007/978-1-4614-5836-4_100

Cited by 1 publication

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, oligomeric structures produced from α-synuclein inclusions have been shown to be structurally related to amyloid beta peptide fibrils found in Alzheimer’s disease [ 56 ]. This may indicate some common iron-mediated neurodegenerative pathway [ 57 , 58 , 59 ]. In addition, an oxidative environment supports the aggregation of α-synuclein, thereby exacerbating the neurodegenerative pathology load [ 60 , 61 ].…”

Section: Typical Features Of Parkinson’s Diseasementioning

confidence: 99%

“…NM exerts a malevolent role. Indeed, it can offer cellular protection by chelating iron and thereby blocking iron-mediated ROS (reactive oxygen species) production and cytotoxic processes such as OS [ 58 , 81 ]. However, this process might be limited by the iron-binding capacity of NM, and as toxic compounds accumulate in the cytosol, a release of iron from NM has been suggested.…”

Section: Risk Factors For Pdmentioning

confidence: 99%

See 1 more Smart Citation

The Nigral Coup in Parkinson’s Disease by α-Synuclein and Its Associated Rebels

Sian-Hülsmann

Riederer

2021

Cells

Self Cite

View full text Add to dashboard Cite

The risk of Parkinson’s disease increases with age. However, the etiology of the illness remains obscure. It appears highly likely that the neurodegenerative processes involve an array of elements that influence each other. In addition, genetic, endogenous, or exogenous toxins need to be considered as viable partners to the cellular degeneration. There is compelling evidence that indicate the key involvement of modified α-synuclein (Lewy bodies) at the very core of the pathogenesis of the disease. The accumulation of misfolded α-synuclein may be a consequence of some genetic defect or/and a failure of the protein clearance system. Importantly, α-synuclein pathology appears to be a common denominator for many cellular deleterious events such as oxidative stress, mitochondrial dysfunction, dopamine synaptic dysregulation, iron dyshomeostasis, and neuroinflammation. These factors probably employ a common apoptotic/or autophagic route in the final stages to execute cell death. The misfolded α-synuclein inclusions skillfully trigger or navigate these processes and thus amplify the dopamine neuron fatalities. Although the process of neuroinflammation may represent a secondary event, nevertheless, it executes a fundamental role in neurodegeneration. Some viral infections produce parkinsonism and exhibit similar characteristic neuropathological changes such as a modest brain dopamine deficit and α-synuclein pathology. Thus, viral infections may heighten the risk of developing PD. Alternatively, α-synuclein pathology may induce a dysfunctional immune system. Thus, sporadic Parkinson’s disease is caused by multifactorial trigger factors and metabolic disturbances, which need to be considered for the development of potential drugs in the disorder.

show abstract