Nervous System

Brief Introduction of Nervous System Diseases

The nervous system consists primarily of two main parts: the central nervous system (CNS) and the peripheral nervous system (PNS). The central system is the body's main command center, composed of the brain and spinal cord. The peripheral nervous system is made up of neural networks that connect the rest of the body to the central nervous system. The main role of the nervous system is to send, receive, and interpret information from all parts of the body, controlling both voluntary and involuntary actions of the human body. Nervous system disorders/diseases cause abnormalities in the nerves, spinal cord, or brain. Nervous system diseases are not rare and affect millions of people worldwide every year. Common nervous system disorders include Alzheimer's disease, strokes, multiple sclerosis, and epilepsy.

Fig.1 A schematic for the nervous system.

Parkinson's disease

Parkinson's disease is a long-term degenerative disease of the central nervous system that results from damage to nerve cells in the brain. This disease mainly affects the smooth control of muscles and movement. The most obvious early symptoms include tremor, stiffness, slowness of movement, and difficulty walking. Sometimes, cognition and behavior are also influenced.

Alzheimer's disease

Alzheimer's disease is a nervous system disease that affects brain function, memory, and behavior. This disease attacks the cells in the brain, causing them to degenerate until they die. There is no permanent cure for this disease, but drugs and therapies can temporarily delay symptoms.

Strokes

Stroke affects the arteries leading to and within the brain. When a blood vessel that carries oxygen and nutrients to the brain is either blocked by a clot or bursts, a stroke occurs. Stroke is the fifth cause of death and a leading cause of disability in the US. It is evaluated about 795,000 people suffer from strokes each year in the US.

Multiple sclerosis

Multiple sclerosis is a very serious disorder of the nervous system. It is characterized as the insulating cover of the nerves degenerates in the nervous system. Depending on the site of the degeneration, patients may suffer from loss of sensory perception, paralysis, or other sensory disturbances.

Epilepsy

Epilepsy is one of the most severe central nervous system diseases. It causes seizures or periods of unusual behavior, sensations, and sometimes loss of awareness. This disease can be inherited or caused by a head injury.

Cerebral palsy

Cerebral palsy is a group of permanent movement disorders that affects the nervous system, muscle control, movement, and coordination. This disease appears in early childhood. Common symptoms include poor coordination, stiff muscles, weak muscles, and tremors.

iPSC and Neurological Diseases

iPSC-based disease modeling provides a useful tool for studying the pathological mechanisms of neurological diseases and developing potential therapeutic drugs for the treatment of neurological diseases. iPSC-based disease modeling starts from the generation of iPSCs from somatic cells such as fibroblasts from a patient individual. Then, these iPSCs can be induced to differentiate into cell types relevant to the diseases, which tremendously contribute to our understanding of neurological diseases. Specifically, through comparison with healthy iPSC-derived nerve cells, patient iPSC-derived nerve cells can be used for identifying disease phenotypes at different levels, including cellular features, molecular profiles, and physiological functionality.

Fig.2 A schematic for iPSC modeling of neurological diseases. (Li, 2018)

iPSC-derived neural stem cells have been applied to demonstrate complex chromosomal changes in neurological diseases. A study showed the detailed mechanism of schizophrenia by using neural stem cells derived from iPSCs and found the upregulation of TLX in the neural stem cells derived from schizophrenia induced changes in miR219 biogenesis, leading to the reduction of neural stem cell proliferation, which may be one of the reasons for the pathogenesis of schizophrenia.

iPSC-derived motor neurons from amyotrophic lateral sclerosis (ALS) patients have been utilized to model ALS in vitro. The diverse phenotypes of familial ALS were observed by using iPSC-derived motor neurons from familial ALS patients, such as mitochondrial dysfunctions and neurite degeneration. Since the death of DA neurons is considered to be the main cause of loss of motor control in Parkinson's disease, iPSC-derived DA neurons were used to construct models of sporadic and familial Parkinson's disease. Many genetic factors related to Parkinson's disease have been identified using iPSC-derived neurons, including LRRK2, PARK2, and PINK1 in familial Parkinson's disease, and GBA1 SCNA SNP in sporadic Parkinson's disease.

Table.1 Neurodegenerative specific iPSC for disease modeling. (Maria, 2016)

iPSC-based neurological disease models provide a useful tool for uncovering disease mechanisms and developing therapeutic strategies to treat them. If you are interested in iPSC-based neurological disease modeling, please contact us for more details.

References

1. Li, L.; et al. Modeling neurological diseases using iPSC-derived neural cells. Cell & Tissue Research. 2018, 371(1):143-151.
2. Maria, G.C.; et al. Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications. Stem Cells Int. 2016, 2016: 4869071.

For Research Use Only. Not For Clinical Use.