Linking pathways in the developing and aging brain with neurodegeneration.
The molecular and cellular mechanisms, which coordinate the critical stages of brain development to reach a normal structural organization with appropriate networks, are progressively being elucidated. Experimental and clinical studies provide evidence of the occurrence of developmental alterations induced by genetic or environmental factors leading to the formation of aberrant networks associated with learning disabilities. Moreover, evidence is accumulating that suggests that also late-onset neurological disorders, even Alzheimer's disease, might be considered disorders of aberrant neural development with pathological changes that are set up at early stages of development before the appearance of the symptoms. Thus, evaluating proteins and pathways that are important in age-related neurodegeneration in the developing brain together with the characterization of mechanisms important during brain development with relevance to brain aging are of crucial importance. In the present review we focus on (1) aspects of neurogenesis with relevance to aging; (2) neurodegenerative disease (NDD)-associated proteins/pathways in the developing brain; and (3) further pathways of the developing or neurodegenerating brains that show commonalities. Elucidation of complex pathogenetic routes characterizing the earliest stage of the detrimental processes that result in pathological aging represents an essential first step toward a therapeutic intervention which is able to reverse these pathological processes and prevent the onset of the disease. Based on the shared features between pathways, we conclude that prevention of NDDs of the elderly might begin during the fetal and childhood life by providing the mothers and their children a healthy environment for the fetal and childhood development.
Institute of Neurology, Medical University of Vienna, Austria. Electronic address: gabor.kovacs@meduniwien.ac.at.
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Kovacs
Inserm U1141, F-75019 Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, UMRS 676, F-75019 Paris, France; Department of Pathology, Lariboisière Hospital, APHP, Paris, France.
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Adle-Biassette
Institute of Neurology, Medical University of Vienna, Austria.
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Milenkovic
Inserm U1141, F-75019 Paris, France.
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Cipriani
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, The Netherlands.
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van Scheppingen
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands; SEIN - Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, The Netherlands.
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Aronica
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D055495:Neurogenesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
brain; development; developmental pathways; human; neurodegeneration; neurodegenerative disease-associated proteins