M. Flint Beal
Cornell University
H-index: 190
North America-United States
Description
M. Flint Beal, With an exceptional h-index of 190 and a recent h-index of 74 (since 2020), a distinguished researcher at Cornell University, specializes in the field of mitochondria, oxidative damage.
His recent articles reflect a diverse array of research interests and contributions to the field:
The role of mitochondrial dysfunction in Alzheimer's disease pathogenesis
Modulation of mitochondrial and inflammatory homeostasis through RIP140 is neuroprotective in an adrenoleukodystrophy mouse model
Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease
Mitochondrial dysfunction and energy metabolism in amyotrophic lateral sclerosis
Isotope-reinforced polyunsaturated fatty acids improve Parkinson’s disease-like phenotype in rats overexpressing α-synuclein
Changes of coenzyme A and acetyl-coenzyme A concentrations in rats after a single-dose intraperitoneal injection of hepatotoxic thioacetamide are not consistent with rapid recovery
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
High‐dose biotin restores redox balance, energy and lipid homeostasis, and axonal health in a model of adrenoleukodystrophy
Professor Information
University | Cornell University |
---|---|
Position | Professor of Neurology, Weill Cornell |
Citations(all) | 130530 |
Citations(since 2020) | 23542 |
Cited By | 113721 |
hIndex(all) | 190 |
hIndex(since 2020) | 74 |
i10Index(all) | 592 |
i10Index(since 2020) | 350 |
University Profile Page | Cornell University |
Research & Interests List
mitochondria
oxidative damage
Top articles of M. Flint Beal
The role of mitochondrial dysfunction in Alzheimer's disease pathogenesis
To promote new thinking of the pathogenesis of Alzheimer's disease (AD), we examine the central role of mitochondrial dysfunction in AD. Pathologically, AD is characterized by progressive neuronal loss and biochemical abnormalities including mitochondrial dysfunction. Conventional thinking has dictated that AD is driven by amyloid beta pathology, per the Amyloid Cascade Hypothesis. However, the underlying mechanism of how amyloid beta leads to cognitive decline remains unclear. A model correctly identifying the pathogenesis of AD is critical and needed for the development of effective therapeutics. Mitochondrial dysfunction is closely linked to the core pathological feature of AD: neuronal dysfunction. Targeting mitochondria and associated proteins may hold promise for new strategies for the development of disease‐modifying therapies. According to the Mitochondrial Cascade Hypothesis, mitochondrial …
Authors
Theophania Ashleigh,Russell H Swerdlow,M Flint Beal
Journal
Alzheimer's & Dementia
Published Date
2023/1
Modulation of mitochondrial and inflammatory homeostasis through RIP140 is neuroprotective in an adrenoleukodystrophy mouse model
Aims Mitochondrial dysfunction and inflammation are at the core of axonal degeneration in several multifactorial neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. The transcriptional coregulator RIP140/NRIP1 (receptor‐interacting protein 140) modulates these functions in liver and adipose tissue, but its role in the nervous system remains unexplored. Here, we investigated the impact of RIP140 in the Abcd1− mouse model of X‐linked adrenoleukodystrophy (X‐ALD), a genetic model of chronic axonopathy involving the convergence of redox imbalance, bioenergetic failure, and chronic inflammation. Methods and results We provide evidence that RIP140 is modulated through a redox‐dependent mechanism driven by very long‐chain fatty acids (VLCFAs), the levels of which are increased in X‐ALD. Genetic inactivation of RIP140 prevented mitochondrial …
Authors
Pablo Ranea‐Robles,Jorge Galino,Lluís Espinosa,Agatha Schlüter,Montserrat Ruiz,Noel Ylagan Calingasan,Francesc Villarroya,Alba Naudí,Reinald Pamplona,Isidre Ferrer,M Flint Beal,Manuel Portero‐Otín,Stéphane Fourcade,Aurora Pujol
Journal
Neuropathology and Applied Neurobiology
Published Date
2022
Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease
Abnormalities in brain glucose metabolism and accumulation of abnormal protein deposits called plaques and tangles are neuropathological hallmarks of Alzheimer’s disease (AD), but their relationship to disease pathogenesis and to each other remains unclear. Here we show that succinylation, a metabolism-associated post-translational protein modification (PTM), provides a potential link between abnormal metabolism and AD pathology. We quantified the lysine succinylomes and proteomes from brains of individuals with AD, and healthy controls. In AD, succinylation of multiple mitochondrial proteins declined, and succinylation of small number of cytosolic proteins increased. The largest increases occurred at critical sites of amyloid precursor protein (APP) and microtubule-associated tau. We show that in vitro, succinylation of APP disrupted its normal proteolytic processing thereby promoting Aβ accumulation …
Authors
Yun Yang,Victor Tapias,Diana Acosta,Hui Xu,Huanlian Chen,Ruchika Bhawal,Elizabeth T Anderson,Elena Ivanova,Hening Lin,Botir T Sagdullaev,Jianer Chen,William L Klein,Kirsten L Viola,Sam Gandy,Vahram Haroutunian,M Flint Beal,David Eliezer,Sheng Zhang,Gary E Gibson
Journal
Nature communications
Published Date
2022/1/10
Mitochondrial dysfunction and energy metabolism in amyotrophic lateral sclerosis
This chapter reviews the current evidence supporting the involvement of mitochondria in amyotrophic lateral sclerosis (ALS) and discusses the potential implications in the pathogenesis of this neurodegenerative disease. Morphologic and ultrastructural abnormalities of mitochondria have been observed in autopsies of patients with sporadic disorder (SALS). In eukaryotic cells, superoxide is a normal byproduct of aerobic respiration and it is produced by oxidative phosphorylation in the mitochondria. A development in the field that has helped in shedding some light on the mechanisms of mitochondrial dysfunction caused by mutant SOD1 is the finding that a proportion of SOD1 is localized in the mitochondria. A number of toxic effects of mutated SOD1 have been proposed, including impairment of mitochondrial energy metabolism and apoptosis. Mitochondria are the site of initiation of the intrinsic apoptotic pathway …
Authors
Giovanni Manfredi,M Flint Beal
Published Date
2021/12/24
Isotope-reinforced polyunsaturated fatty acids improve Parkinson’s disease-like phenotype in rats overexpressing α-synuclein
Lipid peroxidation is a key to a portfolio of neurodegenerative diseases and plays a central role in α-synuclein (α-syn) toxicity, mitochondrial dysfunction and neuronal death, all key processes in the pathogenesis of Parkinson’s disease (PD). Polyunsaturated fatty acids (PUFAs) are important constituents of the synaptic and mitochondrial membranes and are often the first molecular targets attacked by reactive oxygen species (ROS). The rate-limiting step of the chain reaction of ROS-initiated PUFAs autoxidation involves hydrogen abstraction at bis-allylic sites, which can be slowed down if hydrogens are replaced with deuteriums. In this study, we show that targeted overexpression of human A53T α-syn using an AAV vector unilaterally in the rat substantia nigra reproduces some of pathological features seen in PD patients. Chronic dietary supplementation with deuterated PUFAs (D-PUFAs), specifically 0.8 …
Authors
M Flint Beal,Jayandra Chiluwal,Noel Y Calingasan,Ginger L Milne,Mikhail S Shchepinov,Victor Tapias
Journal
Acta Neuropathologica Communications
Published Date
2020/12
Changes of coenzyme A and acetyl-coenzyme A concentrations in rats after a single-dose intraperitoneal injection of hepatotoxic thioacetamide are not consistent with rapid recovery
Small biomolecules, such as coenzyme A (CoA) and acetyl coenzyme A (acetyl-CoA), play vital roles in the regulation of cellular energy metabolism. In this paper, we evaluated the delayed effect of the potent hepatotoxin thioacetamide (TAA) on the concentrations of CoA and acetyl-CoA in plasma and in different rat tissues. Administration of TAA negatively affects liver function and leads to the development of hepatic encephalopathy (HE). In our experiments, rats were administered a single intraperitoneal injection of TAA at doses of 200, 400, or 600 mg/kg. Plasma, liver, kidney, and brain samples were collected six days after the TAA administration, a period that has been suggested to allow for restoration of liver function. The concentrations of CoA and acetyl-CoA in the group of rats exposed to different doses of TAA were compared to those observed in healthy rats. The results obtained indicate that even a single administration of TAA to rats is sufficient to alter the physiological balance of CoA and acetyl-CoA in the plasma and tissues of rats for an extended period of time. The initial concentrations of CoA and acetyl-CoA were not restored even after the completion of the liver regeneration process.
Authors
Yevgeniya I Shurubor,Arthur JL Cooper,Andrey B Krasnikov,Elena P Isakova,Yulia I Deryabina,M Flint Beal,Boris F Krasnikov
Journal
International Journal of Molecular Sciences
Published Date
2020/11/24
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin …
Authors
Stephen C Cunnane,Eugenia Trushina,Cecilie Morland,Alessandro Prigione,Gemma Casadesus,Zane B Andrews,M Flint Beal,Linda H Bergersen,Roberta D Brinton,Suzanne de la Monte,Anne Eckert,Jenni Harvey,Ross Jeggo,Jack H Jhamandas,Oliver Kann,Clothide Mannoury la Cour,William F Martin,Gilles Mithieux,Paula I Moreira,Michael P Murphy,Klaus-Armin Nave,Tal Nuriel,Stéphane HR Oliet,Frédéric Saudou,Mark P Mattson,Russell H Swerdlow,Mark J Millan
Published Date
2020/9
High‐dose biotin restores redox balance, energy and lipid homeostasis, and axonal health in a model of adrenoleukodystrophy
Biotin is an essential cofactor for carboxylases that regulates the energy metabolism. Recently, high‐dose pharmaceutical‐grade biotin (MD1003) was shown to improve clinical parameters in a subset of patients with chronic progressive multiple sclerosis. To gain insight into the mechanisms of action, we investigated the efficacy of high‐dose biotin in a genetic model of chronic axonopathy caused by oxidative damage and bioenergetic failure, the Abcd1− mouse model of adrenomyeloneuropathy. High‐dose biotin restored redox homeostasis driven by NRF‐2, mitochondria biogenesis and ATP levels, and reversed axonal demise and locomotor impairment. Moreover, we uncovered a concerted dysregulation of the transcriptional program for lipid synthesis and degradation in the spinal cord likely driven by aberrant SREBP‐1c/mTORC1signaling. This resulted in increased triglyceride levels and lipid droplets in …
Authors
Stéphane Fourcade,Leire Goicoechea,Janani Parameswaran,Agatha Schlüter,Nathalie Launay,Montserrat Ruiz,Alexandre Seyer,Benoit Colsch,Noel Ylagan Calingasan,Isidre Ferrer,M Flint Beal,Frédéric Sedel,Aurora Pujol
Journal
Brain Pathology
Published Date
2020/9
Professor FAQs
What is M. Flint Beal's h-index at Cornell University?
The h-index of M. Flint Beal has been 74 since 2020 and 190 in total.
What are M. Flint Beal's top articles?
The articles with the titles of
The role of mitochondrial dysfunction in Alzheimer's disease pathogenesis
Modulation of mitochondrial and inflammatory homeostasis through RIP140 is neuroprotective in an adrenoleukodystrophy mouse model
Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease
Mitochondrial dysfunction and energy metabolism in amyotrophic lateral sclerosis
Isotope-reinforced polyunsaturated fatty acids improve Parkinson’s disease-like phenotype in rats overexpressing α-synuclein
Changes of coenzyme A and acetyl-coenzyme A concentrations in rats after a single-dose intraperitoneal injection of hepatotoxic thioacetamide are not consistent with rapid recovery
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
High‐dose biotin restores redox balance, energy and lipid homeostasis, and axonal health in a model of adrenoleukodystrophy
...
are the top articles of M. Flint Beal at Cornell University.
What are M. Flint Beal's research interests?
The research interests of M. Flint Beal are: mitochondria, oxidative damage
What is M. Flint Beal's total number of citations?
M. Flint Beal has 130,530 citations in total.