Neurodegeneration in the context of "Autophagy"

Degenerative 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).

Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process called the Hayflick limit is also known as "replicative senescence", since it is brought about through replication. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress-inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things.

The physiological importance of cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. Senescent cells contribute to the aging phenotype, including frailty syndrome, sarcopenia, and aging-associated diseases. Senescent astrocytes and microglia contribute to neurodegeneration.

Basal ganglia disease is a group of physical problems that occur when the group of nuclei in the brain known as the basal ganglia fail to properly suppress unwanted movements or to properly prime upper motor neuron circuits to initiate motor function. Research indicates that increased output of the basal ganglia inhibits thalamocortical projection neurons. Proper activation or deactivation of these neurons is an integral component for proper movement. If something causes too much basal ganglia output, then the ventral anterior (VA) and ventral lateral (VL) thalamocortical projection neurons become too inhibited, and one cannot initiate voluntary movement. These disorders are known as hypokinetic disorders. However, a disorder leading to abnormally low output of the basal ganglia leads to reduced inhibition, and thus excitation, of the thalamocortical projection neurons (VA and VL) which synapse onto the cortex. This situation leads to an inability to suppress unwanted movements. These disorders are known as hyperkinetic disorders.

Reasons for abnormal increases or decreases of basal ganglia output are not yet well understood. One possible factor could be the natural accumulation of iron in the basal ganglia, causing neurodegeneration due to its involvement in toxic, free-radical reactions. Though motor disorders are the most common associated with the basal ganglia, recent research shows that basal ganglia disorders can lead to other dysfunctions such as obsessive–compulsive disorder (OCD) and Tourette syndrome.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

The major prion protein (PrP) is encoded in the human body by the PRNP gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most prominent in the nervous system but occurs in many other tissues throughout the body.

The protein can exist in multiple isoforms: the normal PrP form, and the protease-resistant form designated PrP such as the disease-causing PrP (scrapie) and an isoform located in mitochondria. The misfolded version PrP is associated with a variety of uniformly fatal neurodegenerative diseases in humans and nonhuman species. In nonhuman species these include ovine scrapie, bovine spongiform encephalopathy (BSE, mad cow disease), feline spongiform encephalopathy, transmissible mink encephalopathy (TME), exotic ungulate encephalopathy, chronic wasting disease (CWD) which affects deer; human prion diseases include Creutzfeldt–Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann–Sträussler–Scheinker syndrome (GSS), kuru, and variant Creutzfeldt–Jakob disease (vCJD). Similarities exist between kuru, thought to be due to human ingestion of diseased individuals, and vCJD, thought to be due to human ingestion of BSE-tainted cattle products.

The National Institute of Neurological Disorders and Stroke (NINDS) is a part of the U.S. National Institutes of Health (NIH). It conducts and funds research on brain and nervous system disorders and has a budget of just over US$2.03 billion. The mission of NINDS is "to reduce the burden of neurological disease—a burden borne by every age group, every segment of society, and people all over the world". NINDS has established two major branches for research: an extramural branch that funds studies outside the NIH, and an intramural branch that funds research inside the NIH. Most of NINDS' budget goes to fund extramural research. NINDS' basic science research focuses on studies of the fundamental biology of the brain and nervous system, genetics, neurodegeneration, learning and memory, motor control, brain repair, and synapses. NINDS also funds clinical research related to diseases and disorders of the brain and nervous system, e.g. AIDS, Alzheimer's disease, epilepsy, muscular dystrophy, multiple sclerosis, Parkinson's disease, spinal cord injury, stroke, and traumatic brain injury.

Established in 1950 by the U. S. Congress as the National Institute of Neurological Diseases and Blindness to help handle the casualties of World War II, NINDS grew along with the NIH. During the 1950s and 1960s, NINDS and the NIH had strong Congressional support and received significant appropriations. However, this funding declined in 1968.

A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.

In the context of neurodegeneration, formation of the glial scar has been shown to have both beneficial and detrimental effects. Particularly, many neuro-developmental inhibitor molecules are secreted by the cells within the scar that prevent complete physical and functional recovery of the central nervous system after injury or disease. On the other hand, absence of the glial scar has been associated with impairments in the repair of the blood brain barrier.