Neuronal cell death and apoptosis in neurodegenerative diseases

Apoptosis is a morphologically defined type of cell death that is distinguished from necrosis. Recently, the hypothesis has been put forward that the progressive death of specific populations of neurons in neurodegenerative diseases occurs by apoptosis. We here review the available data concerning possible apoptotic death of nigral dopaminergic neurons in Parkinson's disease (PD). The presence of apoptotic neurons in the substantia nigra of PD has not been demonstrated unequivocally, This may have technical reasons, but may also be due to the absence of apoptosis. More important than the final mode of cell death, however, is the question whether neurons in neurodegenerative disorders can regain full or partial functional capabilitities. Recent observations in a transgenic mouse model of Huntington's disease showing reversibility of the neurological phenotype by blockade of transgene expression indeed question the principal importance of neuronal cell death for neurodegeneration. These observations rather suggest that at least in early disease stages - neurodegeneration is a reversible process of neuronal cell dysfunction. In this scenario, neuronal cell death does not cause the neurological phenotype, but rather serves to remove non-functional neurons.