Neuropathology of mitochondrial diseases

  title={Neuropathology of mitochondrial diseases},
  author={Massimiliano Filosto and Giuliano Tomelleri and Paola Tonin and Mauro Scarpelli and Gaetano Vattemi and Nicolo’ Rizzuto and Alessandro Padovani and Alessandro Simonati},
  journal={Bioscience Reports},
The term “mitochondrial diseases” (MD) refers to a group of disorders related to respiratory chain dysfunction. Clinical features are usually extremely heterogeneous because MD may involve several tissues with different degrees of severity. Muscle and brain are mostly affected, probably because of their high dependence on oxidative metabolism.Muscle can be the only affected tissue or involved as a part of a multi-system disease; ragged red fibers, accumulation of structurally altered… 
Loss of myelin-associated glycoprotein in kearns-sayre syndrome.
Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination.
Leukoencephalopathies in Mitochondrial Disorders: Clinical and MRI Findings
All MID patients should undergo cerebral imaging even in the absence of clinical CNS manifestations, because the presence of LEM has an impact on the prognosis of an MID.
The neurodegenerative mitochondriopathies.
  • R. Swerdlow
  • Biology
    Journal of Alzheimer's disease : JAD
  • 2009
This review discusses what mitochondrial abnormalities have been identified in various neurodegenerative diseases, what is currently known about the mitochondria-neurodegeneration nexus, and speculates on the significance of mitochondrial function in some disorders not classically thought of as mitochondriopathies.
Age related mitochondrial degenerative disorders in humans
The potential role of mitochondria and mitochondrial DNA mutations in mitochondrial and neurodegenerative diseases, in particular in PD and in AD, are discussed.
The possible involvement of mitochondrial dysfunctions in Lewy body dementia: a systematic review.
It is suggested that mitochondria play an important role in neurodegeneration and a crucial role in the formation of Lewy bodies, a disease characterized by abnormal accumulation of alpha-synuclein that could result in the release of cytochrome c and subsequent activation of the apoptotic cascade.
Neuropathology of Partial PGC-1α Deficiency Recapitulates Features of Mitochondrial Encephalopathies but Not of Neurodegenerative Diseases
It is concluded that the lack of FL-PGC-1α per se is insufficient to recapitulate major features of neurodegenerative diseases, but evokes a pathology seen in mitochondrial encephalopathies, which makes PGC-1 α-deficient mice a valuable model for this yet incurable group of diseases.
Chronic and age-dependent effects of the spongiform neurodegeneration-associated MGRN1 E3 ubiquitin ligase on mitochondrial homeostasis
It is demonstrated that some MGRN1 localizes to mitochondria, most likely due to N-myristoylation, and mitochondria in cells from Mgrn1 null mutant mice display fragmentation and depolarization without recruitment of the parkin E3 ubiquitin ligase.
Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy.
Despite the current hypotheses about myelinic and astrocytic ion-dyshomeostasis underlying white (WM) and grey matter (GM) vacuolation in mitochondrial encephalopathies, there is a paucity of data on
Electron Transport Disturbances and Neurodegeneration: From Albert Szent-Györgyi's Concept (Szeged) till Novel Approaches to Boost Mitochondrial Bioenergetics
Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), a nuclear-encoded master regulator of mitochondrial biogenesis and antioxidant responses in these disorders, may hold novel therapeutic value as a more system-based approach aiming to restore mitochondrial functions in neurodegenerative processes.
Towards Central Nervous System Involvement in Adults with Hereditary Myopathies
This review aims to highlight the character and extent of central nervous system involvement in patients with hereditary myopathies manifesting in adulthood, however also includes some childhood-onset diseases with brain abnormalities that transfer into adult neurological care.


Neuropathology and pathogenesis of mitochondrial diseases
There are some patterns of neuropathology which are characteristic for specific biochemical defects and these may be helpful for diagnosis, in addition to providing detailed information concerning the biological contribution of individual reactions.
Pathology of Mitochondrial Encephalomyopathies
Muscle biopsy provides the best tissue to confirm a mitochondrial cytopathy, and quantitative determinations of respiratory chain enzyme complexes, with citrate synthase as an internal control, confirm the histochemical impressions or may be the only evidence of mitochondrial disease.
Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement
It is proposed that coupling of the vascular mitochondrial dysfunction with cortical spreading depression (CSD) might underlie the selective distribution of ischaemic lesions in the posterior cortex in MELAS patients.
Neuropathological features of mitochondrial disorders.
Application of in situ hybridization and immunohistochemistry to study the choroid plexus and brain-blood barrier in "prototypes" of mitochondrial encephalopathies have revealed alterations that are thought to be important in the pathogenesis of central nervous system dysfunction in these disorders.
Features of cell death in brain and liver, the target tissues of progressive neuronal degeneration of childhood with liver disease (Alpers-Huttenlocher disease)
The presence of both anoxic and apoptotic nuclei in brain and liver, the target tissues of the disease, is consistent with the hypothesis that abnormal activation of mitochondrion-related cell death pathways might be involved in the pathogenesis of AHD.
Neuropathological Aspects of Mitochondrial DNA Disease
Important features from neuropathological studies available are detailed and deficiencies that are currently limiting the understanding of mitochondrial DNA disease are highlighted.
Mitochondrial Encephalomyopathies
It is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of "mitochondrial genetics," including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance.
Familial poliodystrophy, mitochondrial myopathy, and lactate acidemia
This familial multisystem disorder especially involving the brain, skeletal muscle, and heart appears to represent a defect in some mitochondrial oxidative mechanism.
Mitochondrial diseases: a nosological update
An updated classification of mitochondrial diseases is reported, the main clinical syndromes are reviewed, and the most recent genetic knowledge is described.
Mitochondrial diseases.
The principles of mitochondrial genetics are summarized and the common phenotypes, general diagnostic approach, and possible therapeutic venues for these fascinating disorders are discussed.