Springer Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases

Collectively, neurodegenerative diseases are characterized by chronic and progressive loss of neurons in discrete areas of the brain, producing debilitating symptoms such as dementia, loss of memory, loss of sensory or motor capability, decreased overall quality of life eventually leading to premature death. Two types of cell death are known to occur during neurodegeneration: (a) apoptosis and (b) necrosis. The necrosis is characterized by the passive cell swelling, intense mitochondrial damage with rapid loss of ATP, alterations in neural membrane permeability, high calcium influx, and disruption of ion homeostasis. This type of cell death leads to membrane lysis and release of intracellular components that induce inflammatory reactions. Necrotic cell death normally occurs at the core of injury site. In contrast, apoptosis is an active process in which caspases (a group of endoproteases with specificity for aspartate residues in protein) are stimulated. Apoptotic cell death is accompanied by cell shrinkage, dynamic membrane blebbing, chromatin condensation, DNA laddering, loss of phospholipids asymmetry, low ATP levels, and mild calcium overload. This type of cell death normally occurs in penumbral region at the ischemic injury site and in different regions in various neurodegenerative diseases. Review From the reviews: “Farooqui summarizes the current knowledge about neurochemical aspects of trauma such as stroke and head injury and disease such as Alzheimer’s and prion disease. The book can serve as a reference for researchers and clinicians … . chapter projects future directions and developments in the field.” (SciTech Book News, December, 2010) “Readers will find the book to be an excellent source of information about neurochemical changes that occur in many brain diseases. … I can recommend this book to those who work in the field of neurotrauma or to those who are looking for a source of information about the many different neurochemical abnormalities that occur in neurotrauma or in neurodegenerative diseases. … the book fills a major niche in this important area of research.” (David H. Small, Journal of Alzheimer’s Disease, Vol. 24, 2011) From the Back Cover Neurotraumatic (stroke, spinal cord trauma, and traumatic head injury) and neurodegenerative diseases (Alzheimer disease, Parkinson disease, Amyotrophic Lateral Sclerosis, Huntington disease, and prion disease) are afflicting aging Americans with increasing frequency. These diseases result in acute, as well as gradual and progressive neurodegeneration, leading to brain dysfunction. Known risk factors for stroke and neurodegenerative diseases include increasing age, genetic polymorphisms, endocrine dysfunction, oxidative stress, neuroinflammation, excitotoxicity, infection, and exposure to neurotoxins. In contrast, spinal cord trauma and traumatic brain injury due to motorcycle and car accidents are major causes of death and disability among young people below the mid-thirties. Although molecular mechanisms involved in the pathogenesis of neurotraumatic and neurodegenerative diseases remain elusive, oxidative stress, excitotoxicity, inflammation, misfolding, aggregation, and accumulation of proteins, perturbed Ca2+ homeostasis, and apoptosis have been implicated as possible causes of neurodegeneration in the above neurological disorders. In 2005, the global prevalence of neurotraumatic and neurodegenerative diseases was estimated at 35 million, with more than seven million new cases occurring each year. It is calculated that the number of people affected with neurotraumatic and neurodegenerative diseases will double every 20 years, to 100 million by 2040, if a cure is not discovered. More than 60% of dementia cases are due to Alzheimer disease. Today, approximately six million individuals in the US suffer from Alzheimer disease alone, representing one in eight individuals over the age of 65-70. Neurochemical Aspects