Neurodegeneration

This is due to progressive loss of neurons in the CNS, which is irreversible.  However, there are trials being conducted currently to determine whether those neurons can be replaced by the injection/implantation of totipotent (uncommitted) stem cells into the CNS.

The aetiology of neurodegenerative disease is not well understood and may involve both genetic and environmental (lifestyle) factors (therefore mostly idiopathic).  Nevertheless, some mechanisms for neuronal death have been elucidated, including:

• Aberrations in protein folding leading to the formation of non-functional intracellular protein aggregates and cell death.
• Excess glutamate receptor stimulation leading to intracellular Ca2+ overload and cell death.
• Oxidative stress and generation of intracellular free radicals, leading to cellular injury and cell death.
• Aberrations in apoptosis resulting in elevation of programmed cell death.
• Injuries to CNS due to infections, ischaemia, stroke, drug-induced and physical assaults, resulting in neuronal cell death.

The main aim of drug treatment is to relieve the symptoms associated with the neurodegenerative disease.  So far, agents aim to slow or reverse the disease progression (neuroprotective or neurotrophic factors) are still experimental (some in clinical trials).

Dementia/Alzheimer’s Disease

This is due to degeneration of cholinergic neurons in the hippocampus and frontal cortex – areas involved in mood, learning and memory.  The characteristics of this disorder include memory loss, cognitive deficit, reduced learning ability, aggression and mood swing.

The main therapeutic approach is to increase the neurotransmitter acetylcholine in these brain areas:

• Centrally acting reversible anticholinesterases such as donepezil, rivastigmine and galantamine. These agents slow the deterioration of cognitive function but do not reverse or prevent the progression of AD.
• Memantine (a NMDA receptor antagonist). This agent may reduce the glutamate-induced neurodegeneration.
• Other agents can be used to relieved from specific symptoms such as depression and insomnia

Watch the following lecture on Dementia/Alzheimer’s Disease (14 minutes)

 Lecture Notes