The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Linkage Analysis in Italian Pedigrees with Autosomal Dominant Familial Alzheimer\u2019s Disease

In contrast to dementia of the Alzheimer type, the subject of dementia subsequent to cerebral ischemia has been discussed rather rarely. Now this book provides a summary of the brain morphology, neurochemistry and clinical aspects of dementia subsequent to cerebral ischemia. The contributions discuss the similarities and differences between the two predominant dementia types. The broad range of aspects cover 1) the morphology and morphobiology of brain tissue during aging and under the two pathological condi- tions, 2) the neuropathochemistry of post mortem brain tissue of patients as well as brain tissue from experimental animals, 3) CSF changes during aging and in dementia states and 4) clinical research, mainly using brain imaging tech- niques to differentiate between dementia types and to find a basis for rational therapeutic approaches

Growth properties and growth factor responsiveness in skin fibroblasts from centenarians

Human fibroblast cultures, which have a finite replicative lifespan in vitro, are the most widely used model for the study of senescence at the cellular level. An inverse relationship between replicative capability and donor age has been reported in human fibroblast strains. We studied the growth capacity of fibroblast primary cultures derived from people whose lifespan was as closer as possible to the expected maximum human lifespan, i.e. people over one hundred. Our data suggest that outgrowth of fibroblasts from biopsies, growth kinetics at different population doubling levels, capability to respond to a classical mitogenic stimulus (such as 20% serum) and a variety of growth factors, were remarkably similar in fibroblasts from centenarians and young controls. On the whole, our data challenge the tenet of a simple and strict relationship between in vivo aging and in vitro proliferative capability of human fibroblasts, at least at the individual level

Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?

Traumatic brain injury (TBI) has devastating acute effects and in many cases seems to initiate long-term neurodegeneration. Indeed, an epidemiological association between TBI and the development of Alzheimer's disease (AD) later in life has been demonstrated, and it has been shown that amyloid-β (Aβ) plaques — one of the hallmarks of AD — may be found in patients within hours following TBI. Here, we explore the mechanistic underpinnings of the link between TBI and AD, focusing on the hypothesis that rapid Aβ plaque formation may result from the accumulation of amyloid precursor protein in damaged axons and a disturbed balance between Aβ genesis and catabolism following TBI