Longitudinal Metabolomics in Amyotrophic Lateral Sclerosis Implicates Impaired Lipid Metabolism DOI Creative Commons
Kai Guo, Masha G. Savelieff, Dae‐Gyu Jang

и другие.

Annals of Neurology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Objective Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by altered metabolome and energy homeostasis, manifesting with body mass index changes hypermetabolism—both prognostic of progression survival. The cross‐sectional ALS has been characterized, but longitudinal correlations to functional decline are lacking. Methods We longitudinally evaluated metabolomes from plasma terminal postmortem spinal cord brain motor cortex tissue. constructed 3 models. A linear mixed effects model correlated all metabolite levels across timepoints their corresponding scores. An interaction predicted change in function baseline metabolites, whereas identified metabolites linked 20% or 50% drop function. In samples, differential onset versus second segments served as surrogate progression. Mendelian randomization assessed potential causality metabolites. Results plasma, models primarily selected lipid sub‐pathways, addition amino acids, xenobiotics, various less frequently pathways. Among lipids, fatty acids sphingomyelins were predominant, along plasmalogens, phosphatidylcholines, lysophospholipids. Sex findings nominal. the cord, sphingomyelin long‐chain saturated monounsaturated more abundant segment tissue, phosphatidylcholines phosphatidylethanolamines abundant. suggested that impaired carnitine short chain acylcarnitine metabolism may be genetically determined ALS, antioxidant derivatives. Interpretation Our suggest metabolomic involving different classes underscore severity ANN NEUROL 2025

Язык: Английский

Amyotrophic lateral sclerosis DOI Creative Commons
Eva L. Feldman, Stephen A. Goutman, Susanne Petri

и другие.

The Lancet, Год журнала: 2022, Номер 400(10360), С. 1363 - 1380

Опубликована: Сен. 15, 2022

Язык: Английский

Процитировано

526
Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis DOI
Stephen A. Goutman, Orla Hardiman, Ammar Al‐Chalabi

и другие.

The Lancet Neurology, Год журнала: 2022, Номер 21(5), С. 480 - 493

Опубликована: Март 22, 2022

Язык: Английский

Процитировано

273
Amyotrophic lateral sclerosis: translating genetic discoveries into therapies DOI
Fulya Akçimen, Elia R. Lopez, John E. Landers

и другие.

Nature Reviews Genetics, Год журнала: 2023, Номер 24(9), С. 642 - 658

Опубликована: Апрель 6, 2023

Язык: Английский

Процитировано

108
Mitochondrial dysfunction in neurodegenerative disorders DOI Creative Commons

Madelyn Klemmensen,

Seth H. Borrowman,

Colin Pearce

и другие.

Neurotherapeutics, Год журнала: 2023, Номер 21(1), С. e00292 - e00292

Опубликована: Дек. 19, 2023

Recent advances in understanding the role of mitochondrial dysfunction neurodegenerative diseases have expanded opportunities for neurotherapeutics targeting mitochondria to alleviate symptoms and slow disease progression. In this review, we offer a historical account biology disease. Additionally, summarize current knowledge normal physiology pathogenesis dysfunction, disease, therapeutics recent therapeutic advances, as well future directions function. A focus is placed on reactive oxygen species their disruption telomeres effects epigenome. The etiology progression Alzheimer's amyotrophic lateral sclerosis, Parkinson's Huntington's are discussed depth. Current clinical trials mitochondria-targeting discussed.

Язык: Английский

Процитировано

69
Therapeutic application of natural products: NAD+ metabolism as potential target DOI
Guo Chen, Qingxia Huang,

Yisa Wang

и другие.

Phytomedicine, Год журнала: 2023, Номер 114, С. 154768 - 154768

Опубликована: Март 13, 2023

Язык: Английский

Процитировано

48
Skeletal muscle in amyotrophic lateral sclerosis DOI Creative Commons
Jeremy M. Shefner, Antonio Musarò, Shyuan T. Ngo

и другие.

Brain, Год журнала: 2023, Номер 146(11), С. 4425 - 4436

Опубликована: Июнь 16, 2023

Abstract Amyotrophic lateral sclerosis (ALS), the major adult-onset motor neuron disease, has been viewed almost exclusively as a disease of upper and lower neurons, with muscle changes interpreted consequence progressive loss neurons neuromuscular junctions. This led to prevailing view that involvement in ALS is only secondary loss. Skeletal reciprocally influence their respective development constitute single functional unit. In ALS, multiple studies indicate skeletal dysfunction might contribute weakness, well final demise junctions neurons. Furthermore, shown participate pathogenesis several monogenic diseases closely related ALS. Here, we move narrative towards better appreciation contributor We review various potential roles cells from passive bystanders active players pathophysiology. also compare other draw perspectives for future research treatment.

Язык: Английский

Процитировано

44
Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS) DOI Creative Commons
Delfina Larrea, Kirstin A. Tamucci, Khushbu Kabra

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 3, 2025

Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here this impairment crosstalk between mitochondria and ER impedes use glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids sustain energy production. Over time, deficiency alters electron flow active/dormant status complex I spinal cord tissues, but not brain. These findings suggest mitochondria-associated membranes (MAM domains) play crucial role regulating cellular glucose metabolism MAM dysfunction may underlie bioenergetic deficits observed ALS. The Amyotrophic Lateral Sclerosis result from disruption membranes. Here, authors show impairs pyruvate, which over time hinders flow.

Язык: Английский

Процитировано

4
Pharmacotherapy for Amyotrophic Lateral Sclerosis: A Review of Approved and Upcoming Agents DOI
Stephen A. Johnson, Ton Fang, Fabiola De Marchi

и другие.

Drugs, Год журнала: 2022, Номер 82(13), С. 1367 - 1388

Опубликована: Сен. 1, 2022

Язык: Английский

Процитировано

60
Nanoparticle-Based Drug Delivery Systems: An Inspiring Therapeutic Strategy for Neurodegenerative Diseases DOI Open Access

Linyan Duan,

Xingfan Li,

Rong Ji

и другие.

Polymers, Год журнала: 2023, Номер 15(9), С. 2196 - 2196

Опубликована: Май 5, 2023

Neurodegenerative diseases are common, incurable neurological disorders with high prevalence, and lead to memory, movement, language, intelligence impairments, threatening the lives health of patients worldwide. The blood–brain barrier (BBB), a physiological between central nervous system peripheral blood circulation, plays an important role in maintaining homeostasis intracerebral environment by strictly regulating transport substances brain. Therefore, it is difficult for therapeutic drugs penetrate BBB reach brain, this affects their efficacy. Nanoparticles (NPs) can be used as drug carriers also known nanoparticle-based delivery systems (NDDSs). These not only increase stability but facilitate crossing through improve In article, we provided overview types administration routes NPs, highlighted preclinical clinical studies NDDSs neurodegenerative diseases, summarized combined strategies management diseases. Finally, prospects challenges recent basic research were discussed. Above all, provide inspiring strategy treatment

Язык: Английский

Процитировано

39
Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy DOI Creative Commons
Hui Wang, Liping Guan, Min Deng

и другие.

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Май 12, 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons in brain and spinal cord. The causes ALS are not fully understood. About 10% cases were associated with genetic factors. Since discovery first familial pathogenic gene SOD1 1993 technology advancement, now over 40 genes have been found. Recent studies identified related including ANXA11, ARPP21, CAV1, C21ORF2, CCNF, DNAJC7, GLT8D1, KIF5A, NEK1, SPTLC1, TIA1, WDR7. These discoveries contribute to better understanding show potential aid development treatments. Besides, several appear be other neurological disorders, such as CCNF ANXA11 linked FTD. With deepening classic genes, rapid progress has made therapies. In this review, we summarize latest on classical clinical trials for these therapies, well recent findings newly discovered genes.

Язык: Английский

Процитировано

39