Neurodegenerative diseaseA neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic.
Protein aggregationIn molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly. Protein aggregates have been implicated in a wide variety of diseases known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease. After synthesis, proteins typically fold into a particular three-dimensional conformation that is the most thermodynamically favorable: their native state.
PrionA prion ˈpriːɒn is a misfolded protein that can transmit its misfoldedness to normal variants of the same protein and trigger cellular death. Prions cause prion diseases known as transmissible spongiform encephalopathies (TSEs) that are transmissible, fatal neurodegenerative diseases in humans and animals. The proteins may misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein. The consequent abnormal three-dimensional structure confers on them the ability to cause misfolding of other proteins.
AmyloidAmyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously healthy proteins lose their normal structure and physiological functions (misfolding) and form fibrous deposits within and around cells.
Protein foldingProtein folding is the physical process where a protein chain is translated into its native three-dimensional structure, typically a "folded" conformation, by which the protein becomes biologically functional. Via an expeditious and reproducible process, a polypeptide folds into its characteristic three-dimensional structure from a random coil. Each protein exists first as an unfolded polypeptide or random coil after being translated from a sequence of mRNA into a linear chain of amino acids.
Degenerative diseaseDegenerative disease is the result of a continuous process based on degenerative cell changes, affecting tissues or organs, which will increasingly deteriorate over time. In neurodegenerative diseases, cells of the central nervous system stop working or die via neurodegeneration. An example of this is Alzheimer's disease. The other two common groups of degenerative diseases are those that affect circulatory system (e.g. coronary artery disease) and neoplastic diseases (e.g. cancers).
Protein tertiary structureProtein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may interact and bond in a number of ways. The interactions and bonds of side chains within a particular protein determine its tertiary structure. The protein tertiary structure is defined by its atomic coordinates. These coordinates may refer either to a protein domain or to the entire tertiary structure.
Tau proteinThe tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene MAPT (microtubule-associated protein tau). They have roles primarily in maintaining the stability of microtubules in axons and are abundant in the neurons of the central nervous system (CNS), where the cerebral cortex has the highest abundance. They are less common elsewhere but are also expressed at very low levels in CNS astrocytes and oligodendrocytes.
GenerationA generation refers to all of the people born and living at about the same time, regarded collectively. It can also be described as, "the average period, generally considered to be about 20–30 years, during which children are born and grow up, become adults, and begin to have children." In kinship terminology, it is a structural term designating the parent-child relationship. It is known as biogenesis, reproduction, or procreation in the biological sciences.
Generation XGeneration X (often shortened to Gen X) is the demographic cohort following the baby boomers and preceding the millennials. Researchers and popular media use the mid-to-late 1960s as starting birth years and the late 1970s to early 1980s as ending birth years, with the generation being generally defined as people born from 1965 to 1980. By this definition and U.S. Census data, there are 65.2 million Gen Xers in the United States as of 2019.
Drug developmentDrug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug.
Intrinsically disordered proteinsIn molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs range from fully unstructured to partially structured and include random coil, molten globule-like aggregates, or flexible linkers in large multi-domain proteins. They are sometimes considered as a separate class of proteins along with globular, fibrous and membrane proteins.
MillennialsMillennials, also known as Generation Y or Gen Y, are the demographic cohort following Generation X and preceding Generation Z. Researchers and popular media use the early 1980s as starting birth years and the mid-1990s to early 2000s as ending birth years, with the generation typically being defined as people born from 1981 to 1996. Most millennials are the children of baby boomers and older Generation X. In turn millennials are often the parents of Generation Alpha.
Drug designDrug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.
Orphan drugAn orphan drug is a pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by the conditions. The conditions that orphan drugs are used to treat are referred to as orphan diseases. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy that depends on the legislation (if there is any) of the country.
Early modern EuropeEarly modern Europe, also referred to as the post-medieval period, is the period of European history between the end of the Middle Ages and the beginning of the Industrial Revolution, roughly the late 15th century to the late 18th century. Historians variously mark the beginning of the early modern period with the invention of moveable type printing in the 1450s, the Fall of Constantinople and end of the Hundred Years’ War in 1453, the end of the Wars of the Roses in 1485, the beginning of the High Renaissance in Italy in the 1490s, the end of the Reconquista and subsequent voyages of Christopher Columbus to the Americas in 1492, or the start of the Protestant Reformation in 1517.
Early modern periodThe early modern period of modern history spans the period after the Late Middle Ages of the post-classical era (1400–1500) to the beginning of the Age of Revolutions (1800). Although the chronological limits of this period are open to debate, the timeframe is variously demarcated by historians as beginning with the fall of Constantinople in 1453, the Renaissance period in Europe and Timurid Central Asia, the end of the Crusades, the Age of Discovery (especially the voyages of Christopher Columbus beginning in 1492 but also Vasco da Gama's discovery of the sea route to India in 1498), and ending around the French Revolution in 1789, or Napoleon's rise to power.
