Cardiolipin, Mitochondria, and Neurological Disease

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Over the past decade, it has become clear that lipid homeostasis is central to cellular metabolism. Lipids are particularly abundant in the central nervous system (CNS) where they modulate membrane fluidity, electric signal transduction, and synaptic stabilization. Abnormal lipid profiles reported in Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI), are further support for the importance of lipid metablism in the nervous system. Cardiolipin (CL), a mitochondria-exclusive phospholipid, has recently emerged as a focus of neurodegenerative disease research. Aberrant CL content, structure, and localization are linked to impaired neurogenesis and neuronal dysfunction, contributing to aging and the pathogenesis of several neurodegenerative diseases, such as AD and PD. Furthermore, the highly tissue-specific acyl chain composition of CL confers it significant potential as a biomarker to diagnose and monitor the progression in several neurological diseases. CL also represents a potential target for pharmacological strategies aimed at treating neurodegeneration. Given the equipoise that currently exists between CL metabolism, mitochondrial function, and neurological disease, we review the role of CL in nervous system physiology and monogenic and neurodegenerative disease pathophysiology, in addition to its potential application as a biomarker and pharmacological target.

Highlights

The central nervous system is rich in lipids that support membrane fluidity, electric signal transduction, and synaptic stabilization.
Cardiolipin (CL) is a mitochondria-exclusive phospholipid essential for mitochondrial morphology, bioenergetics, dynamics, and signaling pathways.
Alterations in brain CL are associated with impaired neuronal function and neurodegeneration.
The highly tissue-specific acyl chain composition of CL confers it significant potential as a biomarker to diagnose and monitor the progression in several neurological diseases.
CL represents a potential target for pharmacological strategies aimed at treating neurodegeneration.

Related collections

Most cited references 126

Record: found
Abstract: found
Article: found

Is Open Access

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Lorenzo Galluzzi, Ilio Vitale, Stuart A. Aaronson … (2018)

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

0 comments Cited 1589 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Parkinson disease

Werner Poewe, Klaus Seppi, Caroline M Tanner … (2017)

Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

0 comments Cited 1017 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Membrane lipids: where they are and how they behave.

Gerrit van Meer, Dennis Voelker, Gerald Feigenson (2008)

Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?

0 comments Cited 843 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Robert D.S. Pitceathly

Journal

Journal ID (nlm-ta): Trends Endocrinol Metab

Journal ID (iso-abbrev): Trends Endocrinol Metab

Title: Trends in Endocrinology and Metabolism

Publisher: Elsevier Science Pub. Co

ISSN (Print): 1043-2760

ISSN (Electronic): 1879-3061

Publication date PMC-release: 1 April 2021

Publication date (Print): April 2021

Volume: 32

Issue: 4

Pages: 224-237

Affiliations

[1 ]Department of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, London, UK

[2 ]Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

[3 ]Department of Neuromuscular Diseases, University College London Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK

[4 ]Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Author notes

[* ]Correspondence: r.pitceathly@ 123456ucl.ac.uk

Article

Publisher Item ID: S1043-2760(21)00026-6

DOI: 10.1016/j.tem.2021.01.006

PMC ID: 8277580

PubMed ID: 33640250

SO-VID: ae3cc948-f6c6-4adf-b019-c58c17972d4d

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Cardiolipin, Mitochondria, and Neurological Disease

Read this article at

Abstract

Highlights

Related collections

Journal of the ASEAN Federation of Endocrine Societies

Most cited references 126

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Parkinson disease

Membrane lipids: where they are and how they behave.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 508

Cited by 43

Most referenced authors 1,843