Mechanizmy patogenetyczne stwardnienia bocznego zanikowego

• Authors: Joanna Iłżecka

Title variants

EN

Pathogenetic mechanisms of amyotrophic lateral sclerosis

• Languages of publication: PL

Abstracts

PL

Stwardnienie boczne zanikowe (SLA) jest chorobą neurozwyrodnieniową, w której dochodzi do uszkodzenia neuronów ruchowych. Patogeneza SLA jest prawdopodobnie wieloczynnikowa, kompleksowa i nie do końca poznana. Mogą w niej uczestniczyć takie mechanizmy, jak: stres oksydacyjny, toksyczność kwasu glutaminowego, dysfunkcja mitochondriów, stres siateczki wewnątrzplazmatycznej, agregacja białek, dysfunkcja cytoszkieletu, zaburzenia transportu aksonalnego, udział komórek glejowych, neurozapalenie, dyskrazja kwasu mlekowego, czynniki genetyczne. Istotną przyczyną stresu oksydacyjnego w SLA są mutacje genu dysmutazy nadtlenkowej 1 (SOD1) prowadzące do zmienionej aktywności enzymu i jego toksyczności. Zmutowany enzym SOD1 bierze udział w reakcjach zapalnych aktywowanych astrocytów i mikrogleju w rdzeniu kręgowym chorych na SLA. Mechanizmy stresu oksydacyjnego i toksyczności glutaminianu są ze sobą sprzężone. Śmierć motoneuronów następuje wskutek aktywacji kaspaz i drogi apoptozy, a uszkodzenie funkcji mitochondriów uczestniczy w tym procesie. Zmiany patomorfologiczne w obrębie siateczki wewnątrzplazmatycznej występują już we wczesnej fazie choroby i wskazują, że stres tej struktury odgrywa istotną rolę w mechanizmie neurodegeneracji w SLA. W chorobie tej występują także nieprawidłowości cytoszkieletu dotyczące neurofilamentów. Zgodnie z hipotezą dyskrazji kwasu mlekowego dysregulacja kanału mięśniowo-neuronalnego kwasu mlekowego prowadzi do stresu komórkowego, toksyczności i postępującego zwyrodnienia. Istotną funkcję w patogenezie SLA mogą także pełnić mutacje genetyczne innych białek niż SOD1.

EN

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, resulting in a damage of motor neurons. Pathogenesis of ALS is most probably multifactorial, complex and not entirely elucidated. It may involve such mechanisms as oxidative stress, toxicity of glutamic acid, dysfunction of the mitochondria, stress of endoplasmic reticulum, aggregation of proteins, dysfunction of the cytoskeleton, disturbed axonal transport, role of glial cells, neuroinflammatory process, lactic acid dyscrasia, and genetic factors. An important cause of oxidative stress in ALS are mutations of superoxide dismutase 1 (SOD1) gene leading to altered activity of the enzyme and its enhanced toxicity. Abnormal SOD1 participates in inflammatory response of activated astrocytes and microglia in the spinal cord of ALS patients. Mechanisms of oxidative stress and glutamate toxicity are coupled together. Death of motor neurons occurs as a result if activation of caspases and apoptosis, while mitochondrial dysfunction merely participates in the process. Pathomorphological alterations within the endoplasmic reticulum are present already at an early phase of the disease and indicate that stress within this structure plays an important role in the ALS-related process of neurodegeneration. Another interesting feature of ALS are alterations of cytoskeleton, concerning mainly neurofilaments. According to the hypothesis of lactic acid dyscrasia, dysregulation of myoneuronal lactic acid channel results in cellular stress, toxicity and progressive degeneration. An important role in the pathogenesis of ALS may be also played by genetic mutations of proteins other than SOD1.

Keywords

EN

aggregation of proteins; agregacja białek; amyotrophic lateral sclerosis; czynniki genetyczne; dysfunkcja mitochondriów; genetic factors; glutamate-related toxicity; mechanizmy patogenetyczne; mitochondrialdysfunction; oxidative stress; pathogenetic mechanisms; stres oksydacyjny; stwardnienie boczne zanikowe; toksyczność glutaminianu

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Aktualności Neurologiczne
• Year: 2012
• Volume: 12
• Issue: 4
• Pages: 222–235

Contributors

author

Joanna Iłżecka

• Samodzielna Pracownia Rehabilitacji Neurologicznej, Uniwersytet Medyczny w Lublinie

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