Cytoskeletal Alterations in Aging and Disease

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About this Research Topic

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Background

The cytoskeleton, composed of microtubules, intermediate filaments and actin filaments, is critical for its role in cellular homeostasis, caliber, polarity and transport. Contrary to what the term ‘skeleton’ implies, it is highly dynamic and constantly adapting to cellular requirements. Posttranslational modifications of cytoskeletal proteins, e.g., acetylation and phosphorylation, establish a ‘code’, which endows the cytoskeletal scaffold with specific and local functionality. Neurons, especially their long processes, are highly dependent on the cytoskeleton as it forms the basis for axonal transport, establishes key structural elements such as the axon initial segment and presynaptic boutons and regulates axon caliber, polarity, action potential propagation and synaptic plasticity. Furthermore, long axons such as those of motor neurons often carry multiple synapses, which require high energy, specialized synaptic components, and well-coordinated axonal transport and synaptic transmission, hence are more susceptible to disruptions in homeostasis. More recently, researchers and clinicians focus on aberrations of the cytoskeleton and mutations in cytoskeletal related genes as causal issues for neurodegenerative conditions. Therefore, cytoskeleton is in a key position due to its widespread distribution, essential functions, and important interactions with key organelles (e.g., mitochondria and endoplasmic reticulum), as well as a potential instructive player in disease like age-related neurodegeneration.

Despite the crucial role the cytoskeleton plays in neuronal homeostasis and function, not much is known about its involvement in the development physiological aging and the development of neurodegenerative conditions. The aim of this Research Topic is to highlight recent advances in cytoskeletal homeostasis and dynamics with a focus on how physiological or pathological changes in cytoskeleton structure, dynamics or posttranslational modifications translate into shaping cell- or tissue-level events during aging or neurodegenerative conditions. We wish to also shed light on recent advances in tools and approaches that allow to analyze cytoskeleton dynamics and modifications in greater detail (e.g., super-resolution or expansion microscopy) or manipulate it with high spatiotemporal resolution, (e.g., optogenetic tools). Special interest is given to translational approaches combining clinical aspects and basic research.

Areas to cover may include:
• Cytoskeletal aberrations in neurodegenerative conditions;
• Cytoskeleton posttranslational modifications during aging and neurodegenerative diseases;
• Cytoskeletal dynamics during aging and disease progression;
• Impact of aging on the neuronal cytoskeleton;
• Advances in methods to study or manipulate the cytoskeleton;
• Translational reports.

Keywords: cytoskeleton, cytoskeletal alterations, aging, neurodegenerative disease

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