Molecular mechanisms of neurodegeneration and neuroprotection—experimental approaches and the diseased brain

Increasing life expectancy is accompanied by a still unavoidable increase in age-dependent diseases such as cerebrovascular accidents and several neurodegenerative disorders. There are estimates that in the developed countries the number of people over 50 will increase by 10% per year within the next few years, and that each 10 years the life expectancy of people who are 65 years old will increase by one year. This challenging perspective indicates that detailed knowledge of the mechanisms of neurodegeneration and neuronal aging as well as pharmacotherapeutical strategies to combat neurodegenerative processes are urgently required.For example it has been estimated that a delay in the onset of Alzheimer’s disease by five years may decrease the number of affected people by half, which further emphasizes the importance and necessity to focus research activities and to link both basic neuroscience with clinically oriented research and human applications. An international conference on ‘Molecular Mechanisms of Neurodegeneration andNeuroprotection’, held in Leipzig in September 2004 and organized by the Study Group Neurochemistry of the German Society for Biochemistry and Molecular Biology (GBM) and supported by the International Society for Neurochemistry (ISN) and the Interdisciplinary Centre for Clinical Research (IZKF) of the University of Leipzig, intended to provide a forum to discuss novel developments in understanding those mechanisms leading to neurodegeneration including Alzheimer, Parkinson, prion diseases, as well as vascular associated alterations and to highlight potential clinical implications and neuroprotection. The scientific contributions presented during the course of this meeting provided the basis for this special issue of the International Journal of Developmental Neuroscience. Understanding the aetiology of major neurodegenerative diseases and identifying ways of early detection have become an increasingly important approach in treatment and prevention of such diseases. It is generally believed that all of the neurodegeneration-inducing insults ultimately lead to the initiation of a common signalling cascade of neuronal cell death, which manifests clinically as losses in distinct neurological functions, and that degenerative events are usually accompanied by counteracting, compensatory regenerative mechanisms. Therefore, elucidation of the common mechanisms underlying neurodegeneration and regeneration would allow establishment of strategies to intervene in the progression of neurodegenerative events and to support regenerative processes. Abnormal interactions and unfolded or misfolded synaptic proteins have been assumed as important pathogenic events resulting in neurodegeneration in a number of neurological disorders such as Alzheimer, Parkinson and prion diseases, by conversion of nontoxic monomers to toxic oligomers and protofibril (see e.g., Hashimoto et al., 2003). Several stress proteins may act as intracellular molecular chaperones and regulate neuronal cell death and loss (see, e.g., Kitamura and Nomura, 2003). Moreover, disturbances in processes such as metal ion homeostasis, signalling deficits, neurotrophic support and activation of apoptotic and neuroinflammatory signalling are major events that have been assumed to be initiated or worsened by a number of environmental and endogenous factors including neuroinflammation and oxidative stress. Oxidative stress is ubiquitously observed hallmark of neurodegenerative disorders. Neuronal cell dysfunction and cell death due to oxidative stress may causally contribute to the pathogenesis of progressive neurodegenerative disorders. (Moosmann and Behl, 2002). Moreover, chronic neuroinflammation is also a characteristic in several neurodegenerative disorders, which arises in response to an underlying pathology, and may contribute to neurodegeneration (McGeer and McGeer, 2003). Particularly important may be the complement proteins, acute phase reactants and inflammatory cytokines. However, many effects of the complement system appear to promote neuronal survival and tissue remodeling, suggesting that activation of the complement system in the brain may provide a better therapeutic rationale than inhibiting it (van Beek et al., 2003). Therefore, antioxidants as well as anti-inflammatory agents are considered a promising approach to slowing the progression and limiting the extent of neuronal cell loss in a number of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease (see, www.elsevier.com/locate/ijdevneu Int. J. Devl Neuroscience 22 (2004) 441–442