β-AMYLOID

Peptide fragment formed through cleavage of membrane-bound amyloid precursor protein that forms large extracellular deposits within the brains of patients with Alzheimer's disease.

β-SHEETS

A type of repetitive secondary structure that is commonly found in folded proteins. b-Sheets are formed of alternating pleated strands linked by hydrogen bonding between the amino and carboxyl groups of the peptide bond. Formation of b-sheets can be stabilized by protein oligomerization or aggregation.

4-HYDROXYNONENOL (4-HNE)

An oxidative lipid by-product that can react with cysteine, lysine or histidine residues within proteins to form 4-HNE-protein conjugates. This can result in inhibition of protein function.

AKINESIA

Lack or paucity of movement.

ALLOGENEIC

A term that denotes subjects, tissues or cells that are of the same species, but are antigenically distinct.

AMYOTROPHIC LATERAL SCLEROSIS

A progressive neurological disease involving degeneration of the motor neurons of the spinal cord and cerebral cortex; also known as Lou Gehrig's disease. This neuron loss causes muscles to weaken and waste away, leading to paralysis.

ATOMIC FORCE MICROSCOPY

A form of microscopy in which a probe is mechanically tracked over a surface of interest in a series of x-y scans. The force found at each coordinate is measured with piezoelectric sensors, providing information about the chemical nature of a surface.

AUTOPHAGY

Vacuolation of a portion of the cell's own cytoplasm within a membrane and its subsequent digestion after fusion with a lysosome.

AUTOZYGOSITY

Homozygosity by virtue of parental descent from a common ancestor.

CAPACITATIVE CALCIUM ENTRY

Calcium influx that occurs in response to the depletion of intracellular calcium stores. Calcium enters the cell through specialized store-operated channels in the plasma membrane, allowing depleted calcium stores in the endoplasmic reticulum to be replenished.

CATALASE

Peroxisomal enzyme that catalyzes the reduction of H₂O₂ to H₂O.

C-JUN N-TERMINAL KINASES

Stress-activated kinases (SAPKs) that are members of the mitogen-activated protein kinase (MAPK) family of proteins. They act as phosphorylation substrates for MAP kinase kinases (MKKs), and phosphorylation results in activation of the DNA transcription factor c-Jun.

DOMINANT NEGATIVE

A mutant molecule that can form a heteromeric complex with the normal molecule, knocking out the activity of the entire complex.

DYSKINESIA

Hyperkinetic and dystonic abnormal involuntary movements and postures.

ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY

When an atom with an unpaired electron is placed in a magnetic field, the spin of the unpaired electron can align, either in the same direction as the field or in the opposite direction. Electron paramagnetic resonance spectroscopy is used to measure the absorption of microwave radiation that accompanies the transition between these two states.

EXECUTIVE FUNCTION

A cluster of high-order capacities, which include selective attention, behavioral planning and response inhibition, and the manipulation of information in problem-solving tasks.

FLUORESCENCE-ACTIVATED CELL SORTING

A method that allows the separation of cells expressing a specific protein by tagging them with a fluorescent antibody against the molecule of interest. A laser beam excites the fluorescent tag, and the emission of light triggers the cell sorting.

GLUTATHIONE (GSH)

The most abundant thiol-reducing agent in cells. GSH is a tripeptide that consists of glutamate, cysteine and glycine.

GLUTATHIONE PEROXIDASE

An enzyme found in the cytoplasm and mitochondria, which acts in concert with GSH to reduce H₂O₂ to H₂O. During this process, GSH is oxidized to produce GSSG.

GLUTATHIONE REDUCTASE (GSHRd)

An NADPH-dependent enzyme that reduces oxidized glutathione (GSSG) to GSH.

HAPLOINSUFFICIENCY

Loss of one copy (one allele) of a gene is sufficient to give rise to disease. Haploinsufficiency implies that no dominant-negative effect of the mutated gene product has to be invoked.

HOMOLOGOUS RECOMBINATION

The substitution of a segment of DNA with one that is identical or almost identical to it. It occurs naturally during meiosis, but can also be used experimentally for gene targeting to modify the sequence of a gene.

ISOGENIC

A term that denotes subjects, tissues or cells that have identical genotypes. It is synonymous with syngeneic.

KNOCK-IN TRANSGENESIS

The insertion of a mutant gene at the exact site of the genome where the corresponding wild-type gene is located. This approach is used to ensure that the effect of the mutant gene is not affected by the activity of the endogenous locus.

KUNITZ-TYPE PROTEASE INHIBITOR DOMAIN

An alternatively transcribed exon within APP that encodes a protease inhibitor.

LATERAL INHIBITION

The process whereby a signal produced by a given cell prevents adjacent cells from acquiring their fate.

LEWY BODIES

Characteristic intracellular proteinaceous inclusions that are formed in the brains of individuals with Parkinson's disease. They contain high levels of the protein a-synuclein.

LOCUS COERULEUS

A nucleus of the brainstem that is the main supplier of noradrenaline to the brain.

LONG-TERM POTENTIATION (LTP)

An enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency (tetanic) stimulation of afferent pathways. It is measured both as the amplitude of excitatory postsynaptic potentials and as the magnitude of the postsynaptic-cell population spike. LTP is most often studied in the hippocampus and is often considered to be the cellular basis of learning and memory in vertebrates.

MISSENSE MUTATION

A mutation that results in the substitution of an amino acid in a protein.

NEUROMELANIN

A dark-brown pigment formed as a by-product of dopamine oxidation within neurons, which is believed to act as a sink for iron.

NEUROSPHERE

Free-floating, spherical aggregates of neural stem cells. Cells in the neurospheres can proliferate in culture while retaining the potency to differentiate into neurons and glia, making them particularly useful for transplantation studies.

NON-CELL AUTONOMOUS

A genetic trait in which genotypically mutant cells cause other cells (regardless of their genotype) to show a mutant phenotype. By contrast, a cell autonomous trait is one in which only genotypically mutant cells show the mutant phenotype.

NUCLEUS BASALIS OF MEYNERT

A telencephalic structure that provides most of the acetylcholine to the cerebral cortex.

POSITIONAL CLONING

A strategy for the identification of disease genes on the basis of marker inheritance data from affected families that does not require any prior knowledge of the underlying biological pathways or gene function (in contrast to 'candidate-gene' approaches). In recent years, a blend of positional cloning and candidate-gene approaches (sometimes referred to as a 'positional-candidate' strategy) has often been used, involving the combined use of data on map location and expected gene function.

POSITRON EMISSION TOMOGRAPHY (PET)

A technique used to measure neural activity by monitoring changes in regional blood flow. PET has good spatial resolution but relatively poor temporal resolution.

RING DOMAIN

One of a class of protein domains that consist of two loops that are held together at their base by cysteine and histidine residues that complex two zinc ions. Proteins that contain domains of this type are known as RING-finger proteins.

SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT)

A method in which images are generated by using radionuclides that emit single photons of a given energy. Images are captured at multiple positions by rotating the sensor around the subject; the three-dimensional distribution of radionuclides is then used to reconstruct the images. SPECT can be used to observe biochemical and physiological processes, as well as the size and volume of structures. Unlike positron emission tomography, SPECT requires the physical alignment of the photons for their detection, resulting in the loss of many available photons and the degradation of the image.

SMALL INTERFERING RNA

RNA that can be used to interfere with normal RNA processing, causing rapid degradation of the endogenous RNA and thereby precluding translation

SOLID-STATE NMR SPECTROSCOPY

Structural method that depends on obtaining a measure of the magnetic moment of atomic nuclei, which is obtained applying an external magnetic field to a substance of interest in a constant radio frequency field. By contrast to solution-state NMR, solid-state NMR is performed on material in the solid state.

SUBSTANTIA NIGRA

A part of the midbrain that contains dopamine-producing neurons and is involved in the regulation of voluntary motor movement.

SUMOYLATION

The attachment of SUMO, a ubiquitin-like modifier protein. But by contrast to ubiquitin, which targets proteins for degradation, SUMO seems to affect the subcellular localization of proteins and enhance their stability.

SUPEROXIDE DISMUTASE (SOD)

Enzyme involved in the reduction of O₂•^- to H₂O₂. Forms of the enzyme include copper- and zinc-containing cytoplasmic SOD (SOD1), manganese-containing mitochondrial SOD (SOD2) and extracellular SOD (SOD3).

X-RAY FIBER DIFFRACTION

Technique that involves the use of X-rays to determine the quasi-atomic structure of a protein fiber. Although the wavelength of X-rays is close to the size of atoms, images are not reconstructed directly from the scattered X-rays, but from diffraction patterns. Diffraction results from the constructive and destructive interference of X-rays as they are reflected off electrons.