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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Offering all the latest in the study of neurodegenerative diseases, this book reviews the molecular events initiated by unfolded or misfolded proteins leading to conformational human diseases, especially those found in Parkinson’s and Alzheimer’s diseases.

Current research suggests that neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jacob may be linked to disorders in protein shape referred to as protein misfolding. Continued study in this area could lead to promising advances in future treatment of these diseases. This groundbreaking text describes the latest findings regarding protein misfolding in the context of it being a marker, and perhaps a cause, in neurodegenerative diseases. Comprehensive coverage includes the diverse biochemical targets/markers for each disease, the currently limited success of drug therapies, and the cutting-edge research that could lead to more promising treatments.

For decades it has been known that structured conformations are important for the proper functioning of most cellular proteins. However, appreciation that protein folding to the functional conformations as well as the structural maintenance of protein molecules are very complex processes has only emerged during the last ten years. The intimate interplay uncovered by this scientific development led us to realize that perturbations of the protein folding process and disturbances of conformational maintenance are major disease mechanisms. This development has given rise to the concept of conformational diseases and the broader signature of protein folding diseases, comprising diseases in which mutations or environmental stresses may result in a partial misfolding that leads then to alternative conformations capable of disturbing cellular processes. This may happen by self-association (aggregation), as in prion and Alzheimer’s diseases, or by incorporation of alternatively folded subunits into structural entities, as in collagen diseases. Another possibility is that folding to the native structure is impaired or abolished, resulting in decreased stea- state levels of the correctly folded protein, as is observed in cystic fibrosis and 1-antitrypsin deficiency, as well as in many enzyme deficiencies. In addition, deficiencies of proteins that are engaged in assisting and supervising protein folding (protein quality control) may impair the folding of many other proteins, resulting in pathological phenotypes. Examples of this are the spastic paraplegia attributable to mutations in mitochondrial protease/chaperone complexes.

Neurodegenerative Disorders as Proteinopathies: Phenotypic Relationships.- Towards a Molecular Classification of Neurodegenerative Disease.- Racial and Ethnic Influences on the Expression of the Genotype in Neurodegenerative Diseases.- Causes and Consequences of Oxidative Stress in Neurodegenerative Diseases.- Early Onset Familial Alzheimer's Disease: Is a Mutation Predictive of Pathology?.- Identification of Genes that Modify the Age of Onset in a Large Familial Alzheimer's Disease Kindred.- Variable Phenotype of Alzheimer's Disease with Spastic Paraparesis.- Presenilin Mutations: Variations in the Behavioral Phenotype with an Emphasis on the Frontotemporal Dementia Phenoytpe.- Frontotemporal Dementias: Genotypes and Phenotypes.- Chromosome 17-Linked Frontotemporal Dementia with Ubiquitin-Positive, tau-Negative Inclusions.- Variations of the Phenotype in Frontotemporal Dementias.- Phenotype/Genotype Correlations in Parkinson's Disease.- Subject Index