|
Pathophysiology Of Parkinson's Disease
The pathophysiology of Parkinson's disease is apoptosis, death of dopaminergic neurons as a result of changes in biological activity in the brain with respect to Parkinson's disease (PD). There are several proposed mechanisms for neuronal apoptosis, death in PD; however, not all of them are well understood. Five proposed major mechanisms for neuronal death in Parkinson's Disease include protein aggregation in Lewy Body, Lewy bodies, disruption of autophagy, changes in cell metabolism or mitochondrial function, neuroinflammation, and blood–brain barrier (BBB) breakdown resulting in vascular leakiness. Protein aggregation The first major proposed cause of neuronal death in Parkinson's disease is the bundling, or oligomerization, of proteins. The protein alpha-synuclein has increased presence in the brains of Parkinson's Disease patients and, as α-synuclein is insoluble, it protein aggregation, aggregates to form Lewy bodies (shown to left) in neurons. Traditionally, Lewy bodies w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biology), morphology) and death. These changes include Bleb (cell biology), blebbing, Plasmolysis, cell shrinkage, Karyorrhexis, nuclear fragmentation, Pyknosis, chromatin condensation, Apoptotic DNA fragmentation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 1,000,000,000, billion cells each day due to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pontine Tegmentum
The pontine tegmentum, or dorsal pons, is the dorsal part of the pons located within the brainstem. The ventral part or ventral pons is known as the basilar part of the pons, or basilar pons. Along with the dorsal surface of the medulla oblongata, it forms part of the rhomboid fossa – the floor of the fourth ventricle. The pontine tegmentum is all the material dorsal from the basilar pons to the fourth ventricle, and includes the reticulotegmental nucleus, the pedunculopontine nucleus, the laterodorsal tegmental nucleus, and several cranial nerve nuclei. It also houses the pontine respiratory group of the respiratory center which includes the pneumotaxic centre, and the apneustic centre. Anatomy The pontine tegmentum contains nuclei of the cranial nerves ( trigeminal (5th), abducens (6th), facial (7th), and vestibulocochlear (8th) and their associated fibre tracts. The dorsal pons also contains the reticulotegmental nucleus, the mesopontine cholinergic system c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autophagy Diagram PLoS Biology
Autophagy (or autophagocytosis; from the Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components. Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells. Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly. Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy. In macroautophagy (the most thoroughly researched form of autophagy), cytoplasmic components (like mitochondr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Programmed Cell Death
Programmed cell death (PCD) sometimes referred to as cell, or cellular suicide is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage during an organism's biological life cycle, lifecycle. For example, the Limb development, differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development. Apoptosis and autophagy are both forms of programmed cell death. Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Necrosis was long seen as a non-physiological process that occurs as a result of infection or injury, but in the 2000s, a form of programmed necrosis, called necroptosis, was recognized as an alternative f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lewy Body
Lewy bodies are the inclusion bodies – abnormal aggregations of protein – that develop inside neurons affected by Parkinson's disease (PD), the Lewy body dementias ( Parkinson's disease dementia and dementia with Lewy bodies (DLB)), and some other disorders. They are also seen in cases of multiple system atrophy, particularly the parkinsonian variant (MSA-P). Lewy bodies appear as spherical masses in the cytoplasm that displace other cell components. For instance, some Lewy bodies tend to displace the nucleus to one side of the cell. There are two main kinds of Lewy bodies – classical and cortical. A classical Lewy body is an eosinophilic cytoplasmic inclusion consisting of a dense core surrounded by a halo of 10 nm wide radiating fibrils, the primary structural component of which is alpha-synuclein (α-synuclein). While similar in many other respects, cortical Lewy bodies are only faintly eosinophilic, do not have a surrounding halo, and do not show a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Non-homologous End Joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. It is called "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair (HDR), which requires a homologous sequence to guide repair. NHEJ is active in both non-dividing and proliferating cells, while HDR is not readily accessible in non-dividing cells. The term "non-homologous end joining" was coined in 1996 by Moore and Haber. NHEJ is typically guided by short homologous DNA sequences called microhomologies. These microhomologies are often present in single-stranded overhangs on the ends of double-strand breaks. When the overhangs are perfectly compatible, NHEJ usually repairs the break accurately. Imprecise repair leading to loss of nucleotides can also occur, but is much more common when the overhangs are not compatible. Inappropriate NHEJ can lead to translocations and telomere fusion, hallmarks of t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. As a result, kinase produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP). These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis. Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups (dephosphorylation). The phosphorylation state of a molecule, whether it ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Damage (naturally Occurring)
Natural DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. DNA damage can occur naturally or via environmental factors, but is distinctly different from mutation, although both are types of error in DNA. DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of base pairs. DNA damages cause changes in the structure of the genetic material and prevents the replication mechanism from functioning and performing properly. The DNA damage response (DDR) is a complex signal transduction pathway which recognizes when DNA is damaged and initiates the cellular response to the damage. DNA damage and mutation have different biological consequences. While most DNA damages can undergo DNA repair, such repair is not 100% efficient. Un-repaired DNA damages accumulate in non-replicating cells, such as cells in the brai ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Repair
DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified in Cell (biology), cells, by internal metabolism, metabolic by-products, and by external ionizing radiation, ultraviolet light, and medicines, resulting in spontaneous DNA damage involving tens of thousands of individual molecular lesions per cell per day. DNA modifications can also be programmed. Molecular lesions can cause structural damage to the DNA molecule, and can alter or eliminate the cell's ability for Transcription (biology), transcription and gene expression. Other lesions may induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells following mitosis. Consequently, DNA repair as part of the DNA damage response (DDR) is constantly active. When normal repair proce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alpha-synuclein
Alpha-synuclein (aSyn) is a protein that in humans is encoded by the ''SNCA'' gene. It is a neuronal protein involved in the regulation of synaptic vesicle trafficking and the release of neurotransmitters. Alpha-synuclein is abundant in the brain, with smaller amounts present in the heart, muscles, and other tissues. Within the brain, it is primarily localized to the axon terminals of presynaptic neurons. There, it interacts with phospholipids and other proteins. Presynaptic terminals release neurotransmitters from specialized compartments called synaptic vesicles, a process essential for neuronal communication and normal brain function. In Parkinson's disease and related synucleinopathies, abnormal, insoluble forms of alpha-synuclein accumulate within neurons as inclusion bodies, inclusions known as Lewy body, Lewy bodies. Mutations in the ''SNCA'' gene are linked to familial forms of Parkinson's disease. During the process of seeded nucleation, alpha-synuclein adopts a cross-be ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neocortex
The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, spatial reasoning, and language. The neocortex is further subdivided into the true isocortex and the proisocortex. In the human brain, the cerebral cortex consists of the larger neocortex and the smaller allocortex, respectively taking up 90% and 10%. The neocortex is made up of six layers, labelled from the outermost inwards, I to VI. Etymology The term is from ''cortex'', Latin, " bark" or "rind", combined with ''neo-'', Greek, "new". ''Neopallium'' is a similar hybrid, from Latin ''pallium'', "cloak". ''Isocortex'' and ''allocortex'' are hybrids with Greek ''isos'', "same", and ''allos'', "other". Anatomy The neocortex is the most developed in its organisation and number of layers, of the cerebral tissues. The neocortex cons ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
