Cellular Biochemistry of Human Disease - Biochemistry of Neurodegeneration

This set of flashcards covers key concepts from the lecture on cellular biochemistry and neurodegeneration, focusing on the nervous system's structure, function, and the biochemical processes involved in human diseases.

What are the two main parts of the nervous system in most animals?

Central nervous system (CNS) and peripheral nervous system (PNS).

What types of nerve fibers are found in the peripheral nervous system?

Afferent (sensory) and efferent (motor) nerve fibers.

What is the main function of oligodendrocytes and Schwann cells?

To wrap around axons and form the myelin sheath.

What are two main types of synapses in the nervous system?

Electrical synapses and chemical synapses.

What neurotransmitter is involved in the 'rest and digest' response?

Acetycholine.

What is gliosis?

An inflammatory response by glial cells when an injury occurs.

What do chemical synapses require for communication?

Neurotransmitters released from pre-synaptic neurons.

Which type of neuron transmits information from the brain to muscles?

Motor neurons.

What is the role of astrocytes in the nervous system?

Metabolic support for neurons, including lactate production.

What is the significance of the myelin sheath?

It insulates axons and enhances the speed of nerve signal transmission.

What are the three neuroanatomical planes of the brain?

Coronal, sagittal, and transverse (horizontal) planes.

What role do microglia play in the nervous system?

They act as immune cells, performing phagocytosis and responding to injury.

What happens during neuroinflammation?

Microglia activate, releasing cytokines that can contribute to further neuronal damage.

What is the relationship between mitochondria and neurodegeneration?

Mitochondrial dysfunction can lead to increased oxidative stress, contributing to neurodegeneration.

In Alzheimer's disease, what are the two primary protein aggregates seen?

Amyloid plaques (extracellular) and neurofibrillary tangles (intracellular).

What does the term 'selective neuronal vulnerability' refer to in neurodegenerative diseases?

Certain neuron populations are affected while others remain spared.

Which protein is primarily involved in Alzheimer's disease pathology and is known to form amyloid aggregates?

Beta-amyloid (Aβ).

What is the function of the Ubiquitin-Proteasome System (UPS)?

To degrade misfolded or damaged proteins.

What physiological role does calcium play in neurons?

It is essential for neurotransmitter release and cellular signaling.

Why do neurons have high energy demands?

To maintain ionic gradients necessary for action potentials and neurotransmission.

What is the role of TDP-43 in neuronal function?

It is an RNA-binding protein that regulates RNA processing.

What is one consequence of RNA-binding protein dysfunction in neurodegenerative diseases?

Inclusion of cryptic exons in mature mRNA leading to abnormal protein production.

How does oxidative stress relate to neurodegenerative diseases?

It contributes to neuronal damage and is often a result of mitochondrial dysfunction.

What type of aggregation do misfolded proteins often form?

Amyloid fibrils characterized by beta-sheet structure.

What is the consequence of excessive microglia activation?

Chronic inflammation that can further damage neurons.

What is the normal physiological function of the Tau protein?

It stabilizes microtubules within neuronal axons, which is essential for structural integrity and transport.

What is the Blood-Brain Barrier (BBB)?

A highly selective semipermeable border of endothelial cells and astrocyte end-feet that separates circulating blood from the brain's extracellular fluid.

What are the gaps in the myelin sheath called?

Nodes of Ranvier.

What is saltatory conduction?

The rapid 'jumping' of an action potential from one node of Ranvier to another along a myelinated axon, significantly increasing signal speed.

Which glial cells are responsible for producing and circulating cerebrospinal fluid (CSF)?

Ependymal cells.

How do electrical synapses differ from chemical synapses in terms of speed?

Electrical synapses are nearly instantaneous because they allow direct ion flow through gap junctions, whereas chemical synapses have a delay due to neurotransmitter release.

What is excitotoxicity?

A pathological process where neurons are damaged or killed by the overactivation of receptors for excitatory neurotransmitters, primarily glutamate.

What is the core structural feature of amyloid aggregates in neurodegenerative diseases?

A cross-\beta sheet structure that makes the fibrils highly stable and resistant to degradation.

What is the 'third' division of the autonomic nervous system often found in the gut?

The enteric nervous system.

What is the process of macroautophagy?

A cellular pathway that sequesters and degrades large protein aggregates and damaged organelles by delivering them to lysosomes.

What constitutes 'grey matter' in the central nervous system?

Neuronal cell bodies, dendrites, synapses, and unmyelinated axons.

What constitutes 'white matter' in the central nervous system?

Mainly bundles of myelinated axons that connect different grey matter areas.

What is the primary excitatory neurotransmitter in the mammalian CNS?

Glutamate.

What is the primary inhibitory neurotransmitter in the adult human brain?

GABA (\gamma-aminobutyric acid).

What is the role of the tripartite synapse?

A concept stating that synaptic transmission involves the pre-synaptic neuron, the post-synaptic neuron, and surrounding astrocytes that modulate the signal.

What is the primary function of the sympathetic nervous system?

It activates the 'fight or flight' response, increasing heart rate and redirecting blood flow to muscles during stress.

What are the specific cell-to-cell connections that form the Blood-Brain Barrier (BBB)?

Tight junctions between endothelial cells of the brain capillaries.

What is the resting membrane potential of a typical neuron?

Approximately -70 mV, maintained by the unequal distribution of ions across the cell membrane.

What protein is the primary component of Lewy bodies in Parkinson's disease?

\alpha-synuclein.

What is the difference between ionotropic and metabotropic receptors?

Ionotropic receptors are ligand-gated ion channels that act quickly, while metabotropic receptors are G-protein coupled receptors that act slowly via second messengers.

What is the role of the Sodium-Potassium Pump (Na^+/K^+-ATPase) in neurons?

It uses ATP to pump three Na^+ ions out and two K^+ ions in, maintaining the concentration gradients and resting potential.

What does the term 'reactive astrogliosis' describe?

The morphological and molecular changes in astrocytes in response to CNS injury, often resulting in a glial scar.

What occurs at the axon hillock?

The summation of graded potentials occurs here; if the threshold is reached, an action potential is ignited.

What is the function of dendritic spines?

Small protrusions on dendrites that increase surface area for receiving synaptic input and compartmentalize biochemical signals.

What is the difference between anterograde and retrograde axonal transport?

Anterograde transport moves materials from the cell body toward the axon terminal (kinesin-mediated), while retrograde transport moves materials toward the cell body (dynein-mediated).

What is a 'refractory period' in the context of an action potential?

A period following an action potential during which a neuron cannot fire another impulse, ensuring one-way signal propagation.

What characterizes Huntington's disease at the genetic level?

An expansion of CAG repeats in the HTT gene, leading to an abnormally long polyglutamine tract in the Huntingtin protein.

What is the function of the Cerebrospinal Fluid (CSF)?

It provides mechanical buoyancy for the brain, removes metabolic waste products, and maintains a stable chemical environment.

What is the difference between a nerve and a tract?

A nerve is a bundle of axons in the peripheral nervous system (PNS), while a tract is a bundle of axons in the central nervous system (CNS).

What is 'synaptic plasticity'?

The ability of synapses to strengthen or weaken over time in response to increases or decreases in their activity, which is the basis for learning and memory.