Neurodegenerative disease

Neurodegenerative diseases are a group of conditions defined by the progressive loss of neurons. This process is known as neurodegeneration. As neurons suffer damage, they may eventually die. This damage can occur at many different levels of the brain's circuitry. It can happen at the molecular level or at a systemic level. Because there is currently no known way to reverse this loss, these diseases are considered incurable. Scientists believe two major factors contribute to this process: oxidative stress and inflammation.

Biomedical research has found many similarities between these different diseases. At the subcellular level, they often involve atypical protein assemblies, which is called proteinopathy. They also share the process of induced cell death. These similarities are important for science. They suggest that a new treatment for one disease might help improve other diseases as well. The scale of these conditions is massive. In 2019, an estimated 55 million people worldwide lived with dementia. Researchers predict this number will rise to 139 million by the year 2050.

Alzheimer's disease is the most common neurodegenerative disease. It is a chronic condition that causes the loss of neurons and synapses. This loss happens in the cerebral cortex and certain subcortical structures. This leads to gross atrophy, or shrinking, of the temporal lobe, parietal lobe, and parts of the frontal cortex. The pathology of Alzheimer's is characterized by amyloid plaques and neurofibrillary tangles. Plaques are made of small peptides called amyloid beta. These come from a larger protein called amyloid precursor protein, or APP. Enzymes like beta secretase and gamma secretase cleave APP into smaller fragments. These fragments then self-assemble into dense extracellular plaques.

Parkinson's disease is the second most common neurodegenerative disorder. It often causes bradykinesia, which is slow movement, as well as rigidity and tremors. This disease is characterized by the death of dopaminergic neurons in the substantia nigra. This is a specific region of the midbrain. In affected neurons, researchers observe alpha-synuclein-ubiquitin complexes in structures called Lewy bodies. It is thought that defects in protein transport machinery, such as RAB1, may play a role. Age remains the main known risk factor for Parkinson's. However, mutations in genes like SNCA, LRRK2, GBA, and MAPT can also increase risk.

Huntington's disease is a rare autosomal dominant disorder. It is caused by mutations in the huntingtin gene, known as HTT. This mutation causes a polyglutamine tract expansion. This results in a mutant version of the huntingtin protein. These mutant proteins form aggregates called inclusion bodies. These inclusion bodies may be directly toxic to cells. They can also damage molecular motors and microtubules. This interferes with axonal transport, which is the movement of materials through the neuron. This interference can prevent the transport of important cargoes like BDNF. The disease often affects the striatum first, leading to movements called chorea.

Multiple sclerosis, or MS, is a chronic demyelinating disease of the central nervous system. It is caused by an autoimmune attack on the body. This attack results in the loss of the myelin sheath on neuronal axons. The myelin sheath acts like insulation for the nerve. When it is lost, the speed of signal transduction decreases. This leads to cognitive and motor impairments. The disease progresses through episodes of increasing inflammation. This happens when antigens like myelin basic protein trigger an autoimmune response. This causes T cells, B cells, and macrophages to cross the blood-brain barrier and attack the myelin.

Other rare diseases also cause significant neurodegeneration. Amyotrophic lateral sclerosis, or ALS, involves the loss of upper and lower motor neurons. In some cases, mutations in the SOD1 gene are found. Research shows that SOD1 mutations may act on astrocytes, which are cells other than neurons. Batten disease is a rare group of lysosomal storage disorders. It is also called neuronal ceroid lipofuscinoses. It is often characterized by early vision loss and seizures. Finally, Creutzfeldt–Jakob disease is a prion disease. In this condition, misfolded proteins called prions aggregate in brain tissue and cause rapid dementia.