Focal aging: Clues from neurodegenerative diseases

Neurons of the central nervous system in genera I do not multiply after bir th. Therefore, no replacement or biological renewal of individual cells aff ected by aging or death is possible. Morphological changes occurring in the aging brain a re found substantially more pronounced in neurodegenerative diseases. Systemic degenerations of selective brain areas in these disorder s, e.g. in Alzheimer's, Parkinson's, Huntington's disease or in amyotrohpic lateral sclerosis, may be considered as models of accelerated aging and ma y allow to study the genetic and environmental influences of selective agin g and cell death in modules of the central nervous system. Although neurode generative diseases are disparate disorders on the basis of their symptomat ology and the anatomic distribution of pathologic lesions, they actually sh are key attributes with respect to biochemical and cellular determinants of selective vulnerability. Most strikingly, many show a conversion of diseas e specific acid 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 neurodegenerati on and neurodegenerative pathology. The pathological process is counterbala nced by protective mechanisms that may loose their efficacy during normal a ging. This could explain the late onset of even the inherited neurodegenera tive disorders. Since the expression of disease-specific proteins is often not restricted to the affected brain areas (as exemplified by the expressio n of polyglutamine containing proteins in trinucleotide repeat disorders in non-affected brain areas and even outside the brain),the anatomical specif icity of the degenerative process may be determined by associated binding p roteins. Therapeutic strategies include the reinforcement of physiological defense mechanisms and intervention at early phases of the pathological bio chemistry of disease specific proteins.