Chapters authored
Alzheimer Disease and Metabolism: Role of Cholesterol and Membrane Fluidity
Part of the book: Understanding Alzheimer's Disease
Genetic, Biochemical and Histopathological Aspects of Familiar Alzheimer's Disease
Part of the book: Alzheimer's Disease
Physiology and Pathology of Neuroimmunology: Role of Inflammation in Parkinson’s Disease
Parkinson’s disease (PD) is a neurodegenerative disease that affects 1% of the population aged 65 and over and is the second most common neurodegenerative disease next to Alzheimer’s disease. Interneuronal proteinaceous inclusions called Lewy bodies (LB) and a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNPC) are the main features of PD pathology. The most common clinical manifestations are rigidity, tremor, bradykinesia, postural instability, sleep disorders, alterations in gait, smell, memory, and dementia. Genetic and environmental factors are involved in PD, and, recently, oxidative stress, proteasome-mediated protein degradation, and inflammation have acquired relevance as major mechanisms of neuronal dysfunction. Increased levels of reactive oxygen and nitrogen species in the brain contribute to greater vulnerability of proteins to nitro-oxidative modification and to greater degrees of aggregation. These protein aggregates contain a variety of proteins of which α-synuclein appears to be the main structural component. Interestingly, α-synuclein can be secreted by neuronal cells and may lead the initiation and the maintenance of inflammatory events through the activation of microglia, which contributes to dopaminergic neuron depletion. New evidence also suggests that PD may be the result of an autoimmune response in which the immune cells recognize the neurons as foreign elements and would act against them, causing their death.
Part of the book: Physiology and Pathology of Immunology
Mitochondrial Aging and Metabolism: The Importance of a Good Relationship in the Central Nervous System
The mitochondrial theory of aging suggests that mitochondria have a decrease in production capacity of adenosine triphosphate (ATP). The question may seem trivial, but it becomes more complex when considering that dysfunctional mitochondria can be eliminated by lysosomal digestion and that cell with dysfunctional mitochondria can undergo the process of apoptosis. In organs with regenerative capacity, like the liver, cell proliferation can almost completely hide mitochondrial dysfunction. However, evidence indicates selective damage in mitochondria during aging, and so the mitochondrial aging theory is gaining recognition and respect. There is solid evidence that accumulated DNA damage in mitochondria is a cause directly related to metabolic disorders such as diabetes and degenerative disorders such as Alzheimer’s disease. The central nervous system is particularly susceptible to oxidative damage due to several factors, among which are its high oxygen consumption, its dependence on aerobic carbohydrate metabolism, and its complex composition of membrane lipids. Free radicals are generated at many cell sites, and the mitochondrial respiratory chain is one of the main sources. While many studies have been conducted in experimental animal models, the results are relevant because at least some of their interventions suggest a directing aim at reducing the effects of aging.
Part of the book: Mitochondrial DNA