Proper neurite formation is essential for appropriate neuronal morphology to develop and defects at this early foundational stage have serious implications for overall neuronal function. Neuritogenesis is tightly regulated by various signaling mechanisms that control the timing and placement of neurite initiation, as well as the various processes necessary for neurite elongation to occur. Kinases are integral components of these regulatory pathways that control the activation and inactivation of their targets. This review provides a comprehensive summary of the kinases that are notably involved in regulating neurite formation, which is a complex process that involves cytoskeletal rearrangements, addition of plasma membrane to increase neuronal surface area, coupling of cytoskeleton/plasma membrane, metabolic regulation, and regulation of neuronal differentiation. Since kinases are key regulators of these functions during neuromorphogenesis, they have high potential for use as therapeutic targets for axon regeneration after injury or disease where neurite formation is disrupted.
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http://dx.doi.org/10.1007/s00018-019-03336-6 | DOI Listing |
Cells
January 2025
Department of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
In neurons, the acquisition of a polarized morphology is achieved upon the outgrowth of a single axon from one of several neurites. Small extracellular vesicles (sEVs), such as exosomes, from diverse sources are known to promote neurite outgrowth and thus may have therapeutic potential. However, the effect of fibroblast-derived exosomes on axon elongation in neurons of the central nervous system under growth-permissive conditions remains unclear.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Background: Neuroimaging-based evidence suggests that changes in cerebral tissue determinants, including axonal density and myelin content, are associated with aging and neurodegenerative diseases. While neuroimaging markers show strong association with physiological changes, direct validation of their specificity remains challenging. Histology provides useful information for validation, however, faces limitations including denaturation of the sample during preparation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Southern California, Los Angeles, CA, USA.
Background: TDP-43 (TAR DNA-binding protein 43) is one of the most frequently observed co-pathologies in Alzheimer's disease (AD). Recognizing the diversity of pathological features in individuals with AD, including the presence of TDP-43, may lead to more personalized and effective treatment approaches. We investigate ante-mortem cortical microstructural changes in MRI with subsequent autopsy confirmation of Alzheimer's disease neuropathological changes (ADNC) with and without TDP-43 comorbidity.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Background: With an aging population, it is essential to identify subtle features of brain pathology - both neurodegenerative and vascular - at an early stage, which may predict risk of future decline. We used diffusion MRI (dMRI) to assess grey matter cortical microstructure and investigate associations with 1) Alzheimer's disease (AD) pathology and 2) mid/late-life vascular risk (as measured by blood pressure (BP)).
Method: 151 asymptomatic individuals from the British 1946 birth cohort underwent combined PET/MR with [18F]florbetapir Aβ-PET at ∼73yrs, and [18F]MK-6240 tau-PET at ∼76yrs.
Alzheimers Dement
December 2024
Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC, Canada.
Background: Our objective was to assess individual and joint relationships between various mesoscale indicators of brain health (e.g., neuronal, metabolic, and vascular integrity) and cognitive function.
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