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Glossary: Key biochemical neurodegenerative terms you need to know

Analytical techniques  


 

Isothermal titration calorimetry (ITC)

Is a technique that measures the heat released or absorbed during a chemical reaction as an intrinsic probe to characterize any chemical process that involves heat changes spontaneously occurring during the reaction.

 

Microfluidic diffusional sizing (MDS)

Characterizes proteins and their interactions in solution based on the size (hydrodynamic radius) of proteins and protein complexes as they diffuse within a microfluidic laminar flow. For more information click here: https://www.fluidic.com/products/fluidity-one-w

 

Microscale thermophoresis (MST)

Is a technique that is based on thermophoresis, the directed movement of molecules in a temperature gradient. This movement depends on a variety of molecular properties such as size, charge, hydration shell and conformation.

 

Surface plasmon resonance (SPR)

Is a technique used to measure biomolecule interactions where polarized light strikes an electrically conducting surface at the interface between two media. This generates electron charge density waves called plasmons, reducing the intensity of reflected light at a specific angle known as the resonance angle, in proportion to the mass on a sensor surface.

 

Drugs


Aducanumab

A human monoclonal antibody that has been studied for the treatment of Alzheimer's disease (AD). The antibody targets aggregated forms of β-amyloid found in the brains of people with Alzheimer’s disease, in the hopes of reducing its build-up.

 

Amantadine

Used in the early stages of Parkinson's disease which affects release and reuptake of dopamine.

 

Benztropine

Oral/ intramuscular drug used to treat movement disorders such as dytonia and Parkinson's disease. Benztropine acts as an anticholinergic agent to block cholinergic activity in the basal ganglia.

 

Biperiden

Used for the adjunctive treatment of all forms of Parkinson's disease: postencephalitic, idiopathic, and arteriosclerotic. Specific mode of action is unknown, but it is thought that this agent partially blocks central (striatal) cholinergic receptors, thereby helping to balance cholinergic and dopaminergic activity.

 

Bromocriptine

Bromocriptine is an ergot derivatve that is an anticholinergic. By bloking acetylcholine it helps decrease muscle stiffness, sweating, and the production of saliva, and helps improve walking ability in people with Parkinson's disease.

 

Carbidopa

Is given to people with Parkinson's disease in order to inhibit DOPA decarboxylase. This is an important enzyme which plays a role in the biosynthesis of L-tryptophan to serotonin and in the biosynthesis of L-DOPA to dopamine.

 

Donepezil

An oral medication give to patients with Alzheimer's disease that aids the cognitive function of those with the disease. Donepezil binds and reversibly inactivates the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This increases acetylcholine concentrations at cholinergic synapses.

 

Edaravone

Is a neuroprotective agent that is able to slow down the progression of ALS. Edaravone is a strong antioxidant that prevents oxidative stress from motor neuron death in ALS patients, thus slowing down the physical function in patients.

 

Entacapone

Entacapone, together with levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson’s disease signs and symptoms for a greater length of time. Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT eliminates biologically active catechols present in catecholamines.

 

Galanthamine

Is taken for the treatment of mild to moderate vascular dementia and Alzheimer's disease. Galantamine inhibits acetylcholinesterase, an enzyme which hydrolyzes acetylcholine. As a result of acetylcholinesterase inhibition, galanthamine increases the availability of acetylcholine for synaptic transmission.

 

Levodopa

Is used in the clinical treatment of Parkinson's disease. Levodopa crosses the blood–brain barrier, whereas dopamine itself cannot. Thus, Levodopa is used to increase dopamine concentrations in the treatment of Parkinson's disease.

 

Riluzole

Is the first drug to be approved by the FDA in the treatment of ALS. Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. Furthermore it protects neurons from glutamate which is theorized to cause nerve damage in ALS patients.

 

Risperdal

An "off-label" treatment of Huntingtion's disease. Its assumed mechanism of action is that it is able to block dopaminergic and serotonergic receptors in the brain, this leads to reduced tremors in patients with Huntington's disease.

 

Rivastigmine

A cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease and Parkinson's disease. Rivastigmine has demonstrated treatment effects on the cognitive, functional, and behavioural problems commonly associated with Alzheimer's disease.

 

Tetrabenazine

Is the first drug to be approved by the FDA for the treatment of Huntington's disease. Is used to treat chorea which is associated with Huntington's disease. It acts as a reversible high affinity inhibitor of monoamine uptake into vesicles of presynaptic neurons.             

Pathologies


Amyotrophic lateral sclerosis (ALS)

ALS is a disease that causes the death of neurons controlling voluntary muscles. It is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size.

 

Dementia

Dementia is the name for a set of symptoms that includes memory loss and difficulties with thinking, problem-solving or language. Dementia develops when the brain is damaged by diseases such as Alzheimer’s disease.

 

Huntington’s disease (HD)

Huntington's disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of cognition. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many people with Huntington disease develop involuntary jerking or twitching movements known as chorea.

 

Motor neurone diseases (MND)

The term Motor Neuron Disease (MND) encompasses several different conditions whose common feature is the premature degeneration of motor neurons. They all cause movement-related symptoms, mainly muscle weakness. Most of these diseases seem to occur randomly without known causes, but some forms are inherited.

 

Parkinson’s disease (PD)

Parkinson's disease is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to insufficient dopamine in this region of the brain. The cause of this cell death is poorly understood, but it involves the build-up of proteins into Lewy bodies in the neurons.

 

Prion disease

Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family of rare progressive neurodegenerative disorders. The causative agents of TSEs are believed to be prions. The term “prions” refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain.

 

Spinal muscular atrophy (SMA)

Spinal muscular atrophy (SMA) is a genetic disease affecting the central nervous system, peripheral nervous system, and voluntary muscle movement.

 

Synucleinopathy

Synucleinopathies are neurodegenerative diseases characterized by the abnormal accumulation of alpha-synuclein aggregates in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).

Proteins


Alpha-synuclein

Is an intrinsically disordered protein predominantly found at the tips of neurons in specialized structures called presynaptic terminals.

 

Amyloid beta protein (Aβ)

Peptides of 36–43 amino acids that are involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP).

 

Tau proteins

Are proteins that stabilize microtubules. Pathologies and dementias of the nervous system such as Alzheimer's disease and Parkinson's disease are associated with tau proteins that have become defective and no longer stabilize microtubules properly.

 

Prion

Is able to convert normal PrPC proteins into the infectious prion isoform by changing their conformation or shape; which in turn, alters the way the proteins interconnect. Although the exact 3D structure of prions is not known, they have a higher proportion of β-sheet structure in place of the normal α-helix structure.

 

Lewy body

Lewy bodies are abnormal aggregations of protein that develop inside nerve cells, contributing to Parkinson's disease. A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin.

 

Neurofibrillary tangles (NFTs)

Are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary marker of Alzheimer's disease.

 

Neuritic plaques

Are extracellular deposits of amyloid beta (Aβ) found in the brain. Degenerative neural structures and an abundance of microglia and astrocytes can be associated with neuritic plaque deposits. These deposits can also be a byproduct of senescence.

 

Dopamine

Is a catecholamine that functions both as a hormone and a neurotransmitter, and plays several important roles in the brain and body. Dopaminergic signaling is associated with reward-motivated behavior and motor control with dysfunction of the dopamine system leading to numerous diseases such as Parkinson’s disease (PD). PD is caused by the loss of dopamine-secreting neurons that leads to motor impairment.

Strutcures of the brain


Amygdala

Is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain. The amygdalae are essential to feel certain emotions and to perceive them in other people.

 

Basal ganglia

The basal ganglia refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions.

 

Caudate nucleus

The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia. It is a key contributer to controlling motor processes.

 

Cerebrum

Forms the majority of the brain and consists of two hemispheres which occupy the entire vault of the cranium and are incompletely separated from each other by a deep median cleft, the longitudinal cerebral fissure.

 

Forebrain

Is the forward-most (rostral) part of the brain. The forebrain controls body temperature, reproductive functions, eating, sleeping, and the display of emotions.

 

Hippocampus

The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation.

 

Motor neuron

These are nerve cells which control the function and activity of muscles by transmitting impulses through the central nervous system and through the peripheral nervous system.

 

Neuron: Axon

The part of the neuron that takes information away from the cell body.

 

Neuron: Cell body

Contains the nucleus, which houses the genetic blueprint that directs and regulates the cell’s activities.

 

Neuron: Dendrites

Are branch-like structures that extend from the cell body and collect information from other neurons.

 

Putamen

Is a round structure located at the base of the forebrain (or telencephalon). The putamen and caudate nucleus together form the dorsal striatum. A primary function of the putamen is to regulate movements at various stages (e.g. preparation and execution) and influence various types of learning.

 

Substantia nigra

Neurons in the substantia nigra produce the neurotransmitter dopamine and are responsible for relaying messages that plan and control body movement.