Neurodegeneration and Neurodegenerative Diseases

Neurodegeneration and Neurodegenerative Diseases

What do we fear the most when we age? Most of us will most like fear the degeneration of our brain power the most. I admit that symptoms like forgetting names or places that I know I knew annoys me a lot. Therefore neurodegenerative disorders are some of the most feared illnesses in our society.

Alzheimer’s disease affects up to 10% of people over 65 years of age. This disease causes the progressive loss of memory and other mental faculties, leaving the individual confused and incompetent to care for him- or herself. Huntington’s disease is another relatively common neurodegenerative disorder. One in ten thousand individuals are affected. People inflicted with this disease make involuntary movements and become serverely emotionally disturbed as well as cognitively impaired. Prion diseases, including Creutzfeldt-Jakob disease, lead to mental and physical decline followed by death.

Many scientists are working and have been working to find a treatment or cure, still, no successful treatments are yet available for any of this diseases but some progress has been made during recent years. Scientific research in this field aims to understand the disease mechanism in order to develop successful treatments and to prevent the onset of symptoms in patients. Particular genetic traits appear to be linked to many of these diseases. For example, the chromosome and gene linked to Huntington’s disease, Freiderich’s ataxia, the prion genes linked to spongiform encephalopathies, as well as the triplet repeat mutations responsible for myotonic dystrophy have all been identified. Model systems in which to test potential therapies and prevention strategies have been developed and are employed to find a cure for this cruel and distressing diseases.

Familiar neurodegenerative disorders are Alzheimer’s, Parkinson’s, Huntington’s and Wilson’s disorders. Table 1 shows a list of autosomal neurodegenerative diseases including what is known about chromosomal linkage, genes, mutations and pathology.

Table 1. Autosomal dominant primary neurodegenerative diseases. Ch, chromosome; PrP, prion protein; T, tangles; LB, Lewy bodies; 1, is present or exists; AD, Alzheimer’s disease; PD, Parkinson’s disease; HD, Huntington’s disease; SOD, superoxide dismutase.

Alzheimer's disease (AD) is the most common form of dementia among older people which is a brain disorder that seriously affects a person's ability to carry out daily activities. AD begins slowly, it first involves the parts of the brain that control thought, memory and language. Over time, symptoms get worse. People may not recognize family members or have trouble speaking, reading or writing. They may forget how to brush their teeth or comb their hair. Later on, they may become anxious or aggressive, or wander away from home. Eventually, they need total care. The disease usually begins after age 60 and the risk of getting it goes up with age. The risk is also higher if a family member has had the disease. No treatment can yet stop the disease.

Amyotrophic lateral sclerosis (ALS) is a disease that attacks nerve cells called neurons in the brain and spinal cord. The job of neurons is to transmit messages from the brain and spinal cord to voluntary muscles - the ones that control arms and legs. At first, this causes mild muscle problems, some people notice trouble when walking or running, writing and may notice speech problems. Eventually they lose strength and cannot move. When the muscles in the chest fail they cannot breathe. A ventilator may help, but most people with ALS die from respiratory failure. The disease usually strikes between age 40 and 60. More men than women get it. No one knows what causes ALS. It can run in families, but usually it strikes at random. There is no cure. Medicines can relieve symptoms and, sometimes, prolong survival.

Friedreich's ataxia is an inherited disease that damages the nervous system. It affects the spinal cord and the nerves that control muscle movement in arms and legs. Symptoms usually begin between the ages of 5 and 15. The main symptom is ataxia, which is trouble coordinating movements. Specific symptoms include difficulty to walk, muscle weakness, speech problems, involuntary eye movements, scoliosis and heart palpitations. People with Friedreich's ataxia usually need a wheelchair 15 to 20 years after symptoms first appear. In severe cases, people become incapacitated. There is no cure.

Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste away. People are born with the defective gene, but symptoms usually don't appear until middle age. Early symptoms of HD may include uncontrolled movements, clumsiness or balance problems. Later, HD can take away the ability to walk, talk or swallow. Some people stop recognizing family members. Others are aware of their environment and are able to express emotions. If one of the parents has Huntington's disease, there is a 50-50 chance of getting it. A blood test can tell if the HD gene is present and if there is a risk to develop the disease. There is no cure. Medicines can help manage some of the symptoms, but cannot slow down or stop the disease.

Lewy body disease is one of the most common causes of dementia in the elderly that causes a loss of mental functions severe enough to affect normal activities and relationships. Lewy body disease happens when abnormal structures, called Lewy bodies, build up in areas of the brain. The disease may cause a wide range of symptoms, including changes in alertness and attention, hallucinations, problems with movement and posture, muscle stiffness, confusion and finally loss of memory. Lewy body disease can be hard to diagnose since it can be confused with Parkinson’s and Alzheimer’s disease. The disease usually begins between the ages of 50 and 85. The disease gets worse over time. There is no cure.

Parkinson's disease affects nerve cells, or neurons, in a part of the brain that controls muscle movement. In Parkinson's, neurons that make a chemical called dopamine die or do not work properly. Dopamine normally sends signals that help coordinate movements. Symptoms of Parkinson's disease may include trembling of hands, arms, legs, jaw and face, stiffness of the arms, legs and trunks, slowness of movement, poor balance and coordination. Parkinson's usually begins around age 60 but can start earlier. It is more common in men than in women. There is no cure for Parkinson's disease.

Spinal muscular atrophy (SMA) attacks nerve cells, called motor neurons, in the spinal cord. These neurons communicate with voluntary muscles. As neurons are lost muscles weaken. This can affect walking, crawling, breathing, swallowing and head and neck control. SMA runs in families. Parents usually have no symptoms, but still carry the gene. There are many types of SMA, and some of them are fatal. Life expectancy depends on the type of disease.

Spinocerebellar ataxia (SCA) a progressive and degenerative genetic disease containes multiple types, each of which could be considered a disease in its own right. The following is a list of some, not all, types of Spinocerebellar ataxia. The first ataxia gene was identified in 1993 for a dominantly inherited type. It was called “Spinocerebellar ataxia type 1" (SCA1). Subsequently, as additional dominant genes were found they were called SCA2, SCA3, etc. Usually, the "type" number of "SCA" refers to the order in which the gene was found. At this time, there are at least 29 different gene mutations which have been found. Many SCAs below fall under the category of polyglutamine diseases, which are caused when a disease-associated protein (i.e. ataxin-1, ataxin-3, etc.) contains a glutamine repeat beyond a certain threshold. In most dominant polyglutamine diseases, the glutamine repeat threshold is approximately 35, except for SCA3 which is beyond 50. Polyglutamine diseases are also known as "CAG Triplet Repeat Disorders" because CAG is the codon which codes for the amino acid glutamine. Many prefer to refer to these also as polyQ diseases since "Q" is the one-letter reference for glutamine.

Spinal and bulbar muscular atrophy (SBMA), also known as spinobulbar muscular atrophy, X-linked bulbo-spinal atrophy, X-linked spinal muscular atrophy type 1 (SMAX1) and Kennedy's disease (KD) — A X-linked, recessive, slow progressing, neurodegenerative disease associated with mutations of the androgen receptor (AR) gene resulting in the impairment of the AR that can be viewed as a variation of the disorders of the androgen insensitivity syndrome (AIS).

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant pinocerebellar degeneration caused by an expansion of a CAG repeat encoding a polyglutamine tract in the atrophin-1 protein. It is also known as Haw River Syndrome and Naito-Oyanagi disease. Although this condition was perhaps first described by Smith et al. in 1958, and several sporadic cases have been reported from Western countries, this disorder seems to be very rare except in Japan.

There are at least eight neurodegenerative diseases that are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. The expanded CAG repeats create an adverse gain-of-function mutation in the gene products. Of these diseases, DRPLA is most similar to Huntington disease.

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