Brain iron deposition and the free radical-mitochondrial theory of ageing

Ageing Research Reviews
H M Schipper

Abstract

The central hypothesis of this paper states that oxidative stress, augmented iron deposition, and mitochondrial insufficiency in the ageing and degenerating CNS constitute a single neuropathological 'lesion', and that the advent of one component of this triad obligates the appearance of the others. Evidence in support of this unifying perspective is adduced from human neuropathological studies, experimental paradigms of ageing-associated neurological disorders, and a comprehensive model of astroglial senescence. A pivotal role for the enzyme, heme oxygenase-1 (HO-1) in consolidating this tripartite lesion in the ageing and diseased CNS is emphasized. The data are discussed in the context of a revised 'free radical-mitochondrial-metal' theory of brain ageing, and some scientific and clinical implications of the latter are considered.

References

Oct 1, 1992·The Journal of Clinical Investigation·J Zhang, C A Piantadosi
Dec 1, 1992·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J McLarenH M Schipper
Jun 1, 1990·Brain Research. Developmental Brain Research·H M SchipperS Reichlin
Jan 1, 1990·Journal of Neural Transmission. Parkinson's Disease and Dementia Section·K JellingerM B Youdim
Dec 1, 1990·Journal of Neuroscience Research·J R ConnorE J Mufson
Jun 22, 1990·The Journal of Comparative Neurology·L J NobleJ A Ellison
Jan 1, 1989·Free Radical Biology & Medicine·R Munday
Jun 1, 1985·Mechanisms of Ageing and Development·H J GertzF Schultz
Oct 1, 1980·American Journal of Ophthalmology·B Woodford, M O Tso
Feb 1, 1995·Molecular and Chemical Neuropathology·M A SmithG Perry
Jan 15, 1993·Science·A VermaS H Snyder
Nov 1, 1994·Biochemical Society Transactions·S E Browne, M F Beal
Jun 1, 1995·Annals of Neurology·H M SchipperE G Stopa
Sep 15, 1994·Genomics·M Corral-DebrinskiD C Wallace
Oct 1, 1993·Biology of Reproduction·J R BrawerH M Schipper
Aug 1, 1993·Neurology·C C HuangD B Calne
Feb 1, 1993·Neurology·M H BhattC D Marsden
Nov 1, 1995·Neurobiology of Aging·M B MydlarskiH M Schipper
Oct 1, 1995·Neuropathology and Applied Neurobiology·S Cissé, H M Schipper

❮ Previous
Next ❯

Citations

May 13, 2011·Acta Neuropathologica·Lisa FellnerNadia Stefanova
May 29, 2009·Journal of Neural Transmission·Claudia FunkeAnne S Soehn
Jun 22, 2010·Journal of Neural Transmission·Hyman M Schipper
Feb 4, 2010·Environmental Monitoring and Assessment·Luis F O SilvaFrans Waanders
Jun 6, 2009·Expert Reviews in Molecular Medicine·Marcelo R Vargas, Jeffrey A Johnson
Sep 4, 2008·Antioxidants & Redox Signaling·Violetta N PivtoraikoJohn J Shacka
Oct 7, 2009·Antioxidants & Redox Signaling·Neena SinghMaradumane L Mohan
Oct 1, 2010·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Jorn-Hon LiuHsiao-Ming Chao
Dec 21, 2006·Topics in Magnetic Resonance Imaging : TMRI·John F SchenckTimothy O'Keefe
Apr 17, 2013·Biochemistry. Biokhimii︠a︡·N K IsaevV G Skrebitsky
Jul 3, 2009·American Journal of Physiology. Renal Physiology·Nader G AbrahamGeorge Drummond
Nov 24, 2011·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Yoshiya Asano
Jun 1, 2008·Biomarkers in Medicine·Hyman M SchipperDavid H Burns
Feb 18, 2010·Future Medicinal Chemistry·Eric MillsHaoxing Xu
Apr 7, 2010·Neurotoxicity Research·Clivia Pazin MiwaMonica R M Vianna
Jun 16, 2011·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Melanie Bilbul, Hyman M Schipper
Sep 21, 2013·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Huamin XuJunxia Xie
Nov 9, 2006·Free Radical Research·Rebecca WidmerTilman Grune
Mar 12, 2015·International Journal of Molecular Sciences·Hyman M Schipper, Wei Song
Jul 13, 2006·Cutaneous and Ocular Toxicology·Hsiao-Ming ChaoKo-Hua Chen
Jun 6, 2013·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Khadijeh JamialahmadiMahmoud Hosseini
May 8, 2007·Journal of Neuropathology and Experimental Neurology·Michael I AssarafHyman M Schipper
Jun 19, 2012·Seminars in Pediatric Neurology·Giovanna ZorziNardo Nardocci
Feb 7, 2009·Medical Hypotheses·Barney E DwyerMark A Smith
Aug 23, 2008·Free Radical Biology & Medicine·Akiva ShohamHyman M Schipper
Apr 22, 2008·Neurobiology of Aging·Olivier C MaesEugenia Wang
Oct 1, 2007·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Hyman M Schipper
Sep 18, 2007·Progress in Neurobiology·Ya Ke, Zhong Ming Qian
Mar 10, 2007·Neurobiology of Aging·Maria Noêmia Martins de LimaNadja Schröder
Nov 25, 2011·International Journal of Stroke : Official Journal of the International Stroke Society·Joanna M WardlawIan J Deary
Nov 4, 2004·NMR in Biomedicine·John F Schenck, Earl A Zimmerman
May 22, 2009·Journal of Neurochemistry·Hyman M SchipperDavid Zeligman
May 23, 2007·Aging Cell·Wulf Dröge, Hyman M Schipper

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal ganglia in Parkinson's disease (MDS)

The basal ganglia is comprised of the neostriatum, the external and internal pallidal segments, the subthalamic nucleus, the substantia nigra pars reticulata, and the pars compacta of the substantia nigra. The basal ganglia circuitry is responsible for the correct execution of voluntary movements and is implicated in Parkinson's disease. Here is the latest research investigating the basal ganglia in Parkinson's disease.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Aging-Associated Metabolic Disorders

Age is associated with many metabolic disorders including cardiovascular diseases, type 2 diabetes, stroke and heart disease. The mediators in aging process have been suggested to play a part in the cellular processes responsible for these metabolic disorders. Here is the latest research on aging-associated metabolic disorders.

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.

Astrocytes & Huntington’s Disease (MDS)

Astrocytes are abundant within the central nervous system and their dysfunction has been thought to be an important contributor to some neurodegenerative diseases, in particular Huntington’s disease. Damage to these cells may make neurons more susceptible to degeneration. Here is the latest research on astrocytes and Huntington’s disease.

ALS: Stress Granules

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by cytoplasmic protein aggregates within motor neurons. TDP-43 is an ALS-linked protein that is known to regulate splicing and storage of specific mRNAs into stress granules, which have been implicated in formation of ALS protein aggregates. Here is the latest research in this field.

Brain Aging

Here is the latest research on intrinsic and extrinsic factors, as well as pathways and mechanisms that underlie aging in the central nervous system.

Basal Forebrain & Food Avoidance

Neurons in the basal forebrain play specific roles in regulating feeding. Here are the latest discoveries pertaining to the basal forebrain and food avoidance.

Astrocytes in Parkinson Disease

Parkinson's disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons. Some PD-genes may be associated with astrocyte dysfunction. Discover the latest research on astrocytes in Parkinson's disease here.

Astrocytes & Amyloid

Astrocytes are thought to play a role in amyloid production and have been implicated in neurodegenerative diseases such as Alzheimer’s disease. Here is the latest research on the relationship between astrocytes and amyloid.

Astrocytes & Huntington’s Disease

Astrocytes are abundant within the central nervous system and their dysfunction has been thought to be an important contributor to some neurodegenerative diseases, in particular Huntington’s disease. Damage to these cells may make neurons more susceptible to degeneration. Here is the latest research on astrocytes and Huntington’s disease.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Alzheimer's Disease: Endosomes

Dysfunctional endosomal trafficking may be associated with Alzheimer’s disease (AD) pathology. Targeting the endosome may advance treatment options for AD. Here is the latest research on endosomes and AD.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

ALS: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.