Neurodegeneration

Neurodegenerative diseases refer to a group of age-associated conditions with progressive loss of neuronal structure and function, often accompanied by aberrant protein accumulation, resulting in cognitive disability, motor deficits and dementia. The four most common neurodegenerative diseases - Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS) - each have different clinical presentations and affect different neuronal populations and brain areas. However, commonalities have been identified between the diseases, suggesting that abnormal protein aggregation and failure of autophagy, mitochondrial dysfunction and oxidative stress, as well as inflammatory environment and reactive microglia contribute to the development of all these diseases.  Learn about Exosomes in Neurodegenerative Disease and their potential as a source of biomarkers for early detection of these diseases.

Most Common Neurodegenerative Diseases and Their Pathologies

Parkinson's Disease

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons, mainly in the substantia nigra. It is defined by the presence of alpha-synuclein aggregates (Lewy bodies) and accumulation of defective mitochondria, leading to neuronal death. PD patients display a variety of motor symptoms such as resting tremors, rigidity and postural instability, along with non-motor symptoms including depression, sleep disorder and olfactory dysfunction. Sporadic forms of the disease constitute more than 90% of cases and the onset occurs over the age of 60. Currently, there is no cure for PD, but its motor symptoms can be alleviated temporarily with dopamine inducing approaches. New therapies concentrate on neuroprotective and disease-modifying strategies.

Major Protein Targets Involved in PD 

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Huntington's Disease

Huntington’s disease (HD) is marked by a progressive degeneration of neurons of the striatum and cortex. The disease is familial and follows an autosomal dominant inheritance pattern. It is characterized by a polyglutamine repeat expansion in the huntingtin protein that results in formation of neuronal inclusions and subsequent neuronal loss. This leads to movement, psychiatric and cognitive impairments. Patients are usually diagnosed at 40 years of age and have life expectancy of around 15 years. Currently, no cure exists for the disease.

Major Protein Targets Involved in HD

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Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS; commonly know as Lou Gehrig's disease) is a disease of degeneration of motor neurons in the brain and the spinal cord. It is the third most common neurodegenerative disease and the most common motor neuron disease. Symptoms include loss of control of muscle movement as well as muscle weakness, atrophy, twitching and cramps. The onset of the disease occurs at approximately 60 years old and patients survive on average three years from diagnosis. Most cases of ALS are sporadic and involve a number of genes, with further genes still likely to be discovered. However, 60% of familial ALS can be attributed to mutations in four genes: SOD1, TDP-43/TARDBP, FUS and C9orf72. Aberrant autophagy and RNA metabolism are two processes heavily implicated in disease progression. Protein aggregates are also a common feature of ALS.

Major Protein Targets Involved in ALS