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Mitochondrial Genes and Neurodegenerative Disease

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Mitochondrial Dysfunction in Neurodegenerative Disorders

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Abstract

Mitochondrial dysfunction is increasingly recognised as a cause of neurodegeneration in both primary mitochondrial diseases and common neurodegenerative diseases, including Parkinson’s, Alzheimer’s and Huntington’s diseases and amyotrophic lateral sclerosis (ALS).

In this chapter, we will focus on the molecular basis of mitochondrial dysfunction and the mechanisms bridging it to neurodegeneration. In the first part, we will summarise some basic concepts of mitochondrial biology. We will then cover paediatric diseases, including different types of encephalopathies, Leigh disease, leukoencephalopathies and a variety of syndromes with peculiar features. Finally, we will cover diseases in adults, including MNGIE disease, Friedreich ataxia and the disorders associated with alterations in mitochondrial dynamics and quality control. These include axonal Charcot–Marie–Tooth neuropathy, hereditary spastic paraplegia, and autosomal dominant optic atrophy, as well as the inherited and idiopathic forms of common neurodegenerative diseases.

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Author information

Authors and Affiliations

  1. Medical Research Council, Mitochondrial Biology Unit, Cambridge, UK

    Carlo Viscomi PhD & Massimo Zeviani MD, PhD

  2. Unit of Child Neurology, IRCCS Foundation Neurological Institute “C. Besta”, Milan, Italy

    Anna Ardissone MD

Authors
  1. Carlo Viscomi PhD
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  2. Anna Ardissone MD
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  3. Massimo Zeviani MD, PhD
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Corresponding author

Correspondence to Massimo Zeviani MD, PhD .

Editor information

Editors and Affiliations

  1. Newcastle University Medical School, Well. Trust Ctr. for Mitochondrial Res., Newcastle upon Tyne, United Kingdom

    Amy K. Reeve

  2. Newcastle University Medical School, Well. Trust Ctr. for Mitochondrial Res., Newcastle upon Tyne, United Kingdom

    Eve M. Simcox

  3. Cell and Developmental Biology, University College London, London, United Kingdom

    Michael R. Duchen

  4. Newcastle University Medical School, Well. Trust Ctr. for Mitochondrial Res., Newcastle upon Tyne, United Kingdom

    Doug M. Turnbull

Glossary

Ataxia

Lack of voluntary coordination of muscle movements that includes gait abnormality

Athetosis

Slow, involuntary, convoluted, movements of the fingers, hands, toes and feet

Coloboma

A hole in one of the structures of the eye (e.g. iris, retina, choroid or optic disc)

Demyelinating polyneuropathy

Neurological disorder characterised by progressive weakness and impaired sensory function in the legs and arms due to the damage to the myelin sheath

Dysarthria

Speech disorder due impaired coordination of movements in the muscles used for speech production

Dysphagia

Difficulty in swallowing

Dystonia

A state of abnormal muscle tone resulting in muscular spasm and abnormal posture

Hyperreflexia

Abnormal reaction of the involuntary (autonomic) nervous system to stimulation

Hypertrichosis

Abnormal amount of hair growing over the body

Hypotonia

Low resistance to stretch of muscles

Leukoencephalopathy

Disease affecting the brain white matter

Megalencephalic leukoencephalopathy

Progressive condition that affects brain development and function, characterised by an enlarged brain

Microangiopathy

Disease affecting small vessels

Myoclonus

Brief, involuntary twitching of a muscle or a group of muscles

Myoglobinuria

Presence of myoglobin in the urine

Nystagmus

Repetitive, uncontrolled movements of the eyes

Ophthalmoplegia

Slowly progressive paralysis of the extraocular muscles

Pes cavus

High arch of the foot

Polyhydramnios

Excessive accumulation of amniotic fluid

Pyramidal signs

Symptoms related to the descending tract originated from pyramidal cells of motor cortex

Quadriparesis

Weakness of the four limbs

Seizures

Symptoms due to abnormal excessive or synchronous neuronal activity in the brain

Spasticity

Abnormal muscle contraction characterised by a combination of paralysis, increased tendon reflex activity and hypertonia

Supratentorial

The brain area located above the tentorium cerebelli, the membranous roof over the cerebellum

T1, T2, T2 FLAIR

Neuroradiological terms that refer to the relaxation times that protons need to revert back to their resting states after the initial pulse at a certain radiofrequency

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Viscomi, C., Ardissone, A., Zeviani, M. (2016). Mitochondrial Genes and Neurodegenerative Disease. In: Reeve, A., Simcox, E., Duchen, M., Turnbull, D. (eds) Mitochondrial Dysfunction in Neurodegenerative Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-28637-2_4

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