title: [Aging in parts? Systemic aging of the nervous system].
abstract: Neurons of the central nervous system in general do not multiply after birth. Therefore, no replacement or biological renewal of individual cells affected by aging or death is possible. Morphological changes occurring in the aging brain are found substantially more pronounced in neurodegenerative diseases. Systemic degenerations of selective brain areas in these disorders, e.g. in Alzheimer's, Parkinson's, Huntington's disease or in amyotrophic lateral sclerosis, may be considered as models of accelerated aging and may allow to study the genetic and environmental influences of selective aging and cell death in modules of the central nervous system. Although neurodegenerative diseases are disparate disorders on the basis of their symptomatology and the anatomic distribution of pathologic lesions, they actually share key attributes with respect to biochemical and cellular determinants of selective vulnerability. Most strikingly, many show a conversion of disease specific and only recently identified proteins into unsoluble aggregates which form intra- or extracellular deposits. These protein aggregates may, over time, affect neuronal function, eventually leading to neurodegeneration and neurodegenerative pathology. The pathological process is counterbalanced by protective mechanisms that may loose their efficacy during normal aging. This could explain the late onset of even the inherited neurodegenerative disorders. Since the expression of disease-specific proteins is often not restricted to the affected brain areas (as exemplified by the expression of polyglutamine containing proteins in trinucleotide repeat disorders in non-affected brain areas and even outside the brain), the anatomical specificity of the degenerative process may be determined by associated binding proteins. Therapeutic strategies include the reinforcement of physiological defense mechanisms and intervention at early phases of the pathological biochemistry of disease specific proteins.
authors.affiliation: Neurologische Klinik der Universität Tübingen.
authors.forename: J
authors.initials: J
authors.lastname: Dichgans
authors.forename: J B
authors.initials: JB
authors.lastname: Schulz
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D002490:Central Nervous System / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins