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J Neural Transm Suppl. 1998;54:147-58.

Aberrancies in signal transduction and cell cycle related events in Alzheimer's disease.

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  • 1Department of Neuroanatomy, Paul Flechsig Institute of Brain Research, University of Leipzig, Federal Republic of Germany.


Neurodegeneration in Alzheimer's disease (AD) is associated with the appearance of dystrophic neuronal growth profiles that most likely reflects an aberrant attempt of neuronal repair. This process of neuronal reorganisation, which eventually goes awry and becomes a disease itself, might be initiated physiologically as a response to neuronal injuries. Minor neuronal damage due to a variety of life events or genetic pertubations that are usually compensated in the normal adult brain by adaptation and repair might thus be amplified and accumulated, thereby resulting in a progressive neurodegeneration. The present paper summarizes recent evidence supporting the hypothesis that a primary impairment of intracellular signal transduction that is mediated by a hierarchy of phosphorylation signals and associated with a aborted attempt of neurons to re-enter the cell-cycle is a key element in the pathomechanism of AD. These changes might result in malfunction of neuronal adaptation and repair and eventually lead to neuronal death. During the process of aging as well as in chronic neurodegenerative disorders such as Alzheimer's disease (AD), the continuous but rather slow action of pathogenetic factors might give room for the activation of compensatory mechanisms, serving to regain a neuronal population much of its synaptic connectivity in the presence of cell loss. An upregulation in the capacity to synthesize and store neurotransmitters (Lapchak et al., 1991), an increased expression of trophic factors (Hellweg et al., 1990; Arendt et al., 1995a,b), as well as regenerative sprouting (Fritschy and Grzanna, 1992), synaptic enlargement (Scheff et al., 1990; Lippa et al., 1992), and neosynaptogenesis (Ramirez and Ulfhake, 1992) have been described among other processes.

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