T2*-weighted MRI values correlate with motor and cognitive dysfunction in Parkinson's disease

Tambasco, Nicola; Paoletti, Federico Paolini; Chiappiniello, Andrea; Lisetti, Viviana; Nigro, Pasquale; Chiarini, P; Romoli, Michele; Brahimi, Elona; Simoni, Simone; Filidei, Marta; Floridi, Piero; Tarducci, R.; Parnetti, Lucilla; Calabresi, Paolo

doi:10.1016/j.neurobiolaging.2019.04.005

Cited by 21 publications

(12 citation statements)

References 52 publications

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“…Significant iron deposition has been detected in the SN pars compacta in PD, and the accumulation of iron is consistent with the progress of PD [87, 88], suggesting that elevated iron levels from various causes may be important in the induction of ferroptosis in PD [89, 90]. Transferrin can serve as a natural ligand for FPN-mediated iron export to deliver and remove iron from cells, and it is found that transferrin has been depleted in PD SN, which may be an important factor for iron accumulation in PD SN [91].…”

Section: The Role Of Ferroptosis In Neurodegenerative Diseasesmentioning

confidence: 94%

Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases

et al. 2020

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Background: Neurodegenerative diseases are characterized by a gradual decline in motor and/or cognitive function caused by the selective degeneration and loss of neurons in the central nervous system, but their pathological mechanism is still unclear. Previous research has revealed that many forms of cell death, such as apoptosis and necrosis, occur in neurodegenerative diseases. Research in recent years has noticed that there is a new type of cell death in neurodegenerative diseases: ferroptosis. An increasing body of literature provides evidence for an involvement of ferroptosis in neurodegenerative diseases. Summary: In this article, we review a new form of cell death in neurodegenerative diseases: ferroptosis. Ferroptosis is defined as an iron-dependent form of regulated cell death, which occurs through the lethal accumulation of lipid-based reactive oxygen species when glutathione-dependent lipid peroxide repair systems are compromised. Several salient and established features of neurodegenerative diseases (including lipid peroxidation and iron dyshomeostasis) are consistent with ferroptosis, which means that ferroptosis may be involved in the progression of neurodegenerative diseases. In addition, as the center of energy metabolism in cells, mitochondria are also closely related to the regulation of iron homeostasis in the nervous system. At the same time, neurodegenerative diseases are often accompanied by degeneration of mitochondrial activity. Mitochondrial damage has been found to be involved in lipid peroxidation and iron dyshomeostasis in neurodegenerative diseases. Key Messages: Based on the summary of the related mechanisms of ferroptosis, we conclude that mitochondrial damage may affect neurodegenerative diseases by regulating many aspects of ferroptosis, including cell metabolism, iron dyshomeostasis, and lipid peroxidation.

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Section: The Role Of Ferroptosis In Neurodegenerative Diseasesmentioning

confidence: 94%

Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases

et al. 2020

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“…S1, S3). Thus, they are expected to be sensitive to age-related iron accumulation in DN ( Zecca et al, 2004a ) and to DN depletion ( Damier et al, 1999b ) and therefore potentially to cognitive and motor impairment in PD ( Tambasco et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Toward an early diagnostic marker of Parkinson’s: measuring iron in dopaminergic neurons with MR relaxometry

Brammerloh

Morawski

Weigelt

et al. 2020

Preprint

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AbstractIn Parkinson’s disease, the depletion of iron-rich dopaminergic neurons in substantia nigra’s nigrosome 1 precedes first motor symptoms by two decades. Monitoring this neuronal depletion at an early disease stage is needed for diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue iron. However, the mechanisms of MRI contrast in substantia nigra are not well understood, hindering the development of specific biomarkers. We showed that the dominant contribution to the effective transverse MRI relaxation rate in nigrosome 1 originates from iron accumulated in the neuromelanin of dopaminergic neurons. We linked quantitatively to the product of cell density and local iron concentration in dopaminergic neurons, combining quantitative 3D iron histology, biophysical modeling, and quantitative MRI on post mortem brain tissue. This knowledge opens an avenue for monitoring neuronal iron and density in vivo and may be applied to detect early neurodegeneration in Parkinson’s disease.

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“…Recent studies on PD patients with cognitive impairment describe increased iron accumulation in the caudate and cortex. [191][192][193] Arguing in favor of a causative role for iron in PD are the observations that direct infusion of Fe 3þ to the SN in rats results in mitochondrial dysfunction, oxidative stress, neuronal loss, striatal dopamine depletion, and impaired motor function, all characteristic features of PD. [194][195][196][197] Administration of MPTP or 6-OHDA to rodents and monkeys also increases iron content in the SN and this increase is proportional to the loss of neurons.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

“…203 Relevant to this point, some human studies have found that the increase of SN iron occurs only in the most severely affected patients. [189][190][191][192][193][194][195] At least one study utilizing monkeys and the MPTP model also found that the increase of iron in the SN occurs only with severe PD pathology and behavioral deficits. 207 Given that the clinical symptoms, neuropathological features, and rate of disease progression display a significant level of variability, it is possible that in a subset of PD cases, iron accumulation may be causally involved in disease progression, whereas it may be associated or result from degeneration in some other cases of PD.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

Overdosing on iron: Elevated iron and degenerative brain disorders

D’Mello¹,

Kindy

2020

Exp Biol Med (Maywood)

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All cells in organisms ranging from yeast to humans utilize iron as a cofactor or structural element of proteins that function in diverse and critical cellular functions. However, deregulation of the homeostatic mechanisms regulating iron metabolism resulting in a reduction or excess of iron within the cell or outside of it can have serious effects to the health of cells and the organism. This review provides a brief overview of the molecular and cellular mechanisms regulating iron physiology, including the molecules and processes regulating iron uptake, its storage and utilization, its recycling, and its release from the cell, such that the cellular iron levels are sufficient to meet metabolic demand but below those that cause permanent damage. The major focus of review is on the pathological consequences of dysregulation of these homeostatic mechanisms, focusing on the brain. Current advances on the role of iron accumulation to the pathogenesis of rare neurological disorders caused by genetic mutations as well as to the more prevalent and age-associated neurodegenerative diseases are described. Impact statement Brain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer’s disease and Parkinson’s disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.

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T2*-weighted MRI values correlate with motor and cognitive dysfunction in Parkinson's disease

Cited by 21 publications

References 52 publications

Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases

Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases

Toward an early diagnostic marker of Parkinson’s: measuring iron in dopaminergic neurons with MR relaxometry

Overdosing on iron: Elevated iron and degenerative brain disorders

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