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ARTICLE | NEUROSCIENCE | Mitochondrial dysfunction is one of the major


causative factors in the ageing process, causing ischaemia/reperfusion phenomenon, septic shock and neurodegenerative alterations such as ParkinsonÕs disease (PD), AlzheimerÕs disease (AD), and HuntingtonÕs disease (HD). However, mitochondrial dysfunction is not only implicated in neurodegenerative disease, but also in diabetes, cardiovascular disease, musculoskeletal conditions, sepsis, hepatic and other disorders that complicate the treatment of each one of the original or main diseases. The number of neurodegenerative diseases is currently estimated to be a few hundred4


.


Neurodegenerative diseases Alzheimer’s disease Worley7


HuntingtonÕs described AD as a Ôdehumanizing condition of


degenerative memory loss and physical deterioration which ultimately leads to deathÕ. More specifically, AD is the most common cause of dementia among older generations, with a clinical presentation that includes, but is not limited to, short- and long-term memory loss, language disparities, the inability to recognise familiar people or places, uncoordinated movements, and poor judgment8


. Although a number of theories of the


pathogenesis of AD abound, there is no unanimously accepted explanation of cause. A range of risk factors have been identified as predisposing entities for AD. According to Yaari and Corey-Bloom8


, a positive family


history is the most prominent risk factor. AD develops slowly. At first it involves the parts of the


brain that control thought, memory and language. People with AD may have trouble remembering things that happened recently or names of people they know. A related problem, mild cognitive impairment (MCI), causes more memory problems compared with people of the same age who do not have AD. Many people with MCI will develop AD.


disease is an inherited disease that causes certain nerve cells in the brain to waste away. People are born with the defective gene, but symptoms do not always appear until later in life.


Over time, symptoms of AD will worsen. People may


not recognise family members or have trouble speaking, reading or writing. Later, they may become anxious or aggressive, or wander away from home. Eventually, they will require total care. This can cause great stress for family members who must care for them. AD usually begins after 60 years, the risk of which increases with age. There is no treatment for AD, but some drugs may help keep symptoms at bay for a limited time.


Parkinson’s disease PD is a disorder that affects nerve cells, or neurons, in the part of the brain that controls muscle movement. In PD, neurons make dopamine die or do not work properly. Dopamine normally sends signals that help coordinate movement. Symptoms of PD may include: ■ Trembling of hands, arms, legs, jaw and face (tremor) ■ Stiffness of the arms, legs and trunk ■ Slowness of movement (bradykinesia) ■ Poor balance and coordination. As symptoms worsen, people with the disease may


have trouble walking, talking or carrying out everyday tasks. They may also experience depression, sleep problems, or trouble chewing, swallowing or speaking. PD usually begins around the age of 60 years, but it can manifest earlier, and is more common in men. There is no cure for PD; however, a variety of medicines can help to reduce symptoms.


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 do not always appear until later in life. Early symptoms of HD may include uncontrolled movements or clumsiness. Later, HD can make walking, talking or swallowing difficult. If one parent has HD, their offspring have a 50-50 chance of inheriting the disease. However, there is no cure. Medicines can help manage some of the symptoms, but cannot slow down or stop the disease.


Causes of neurodegenerative diseases A number of processes produce neural damage: mitochondrial dysfunction, autophagy9 misregulation of protein-210


β-amyloid, α-synuclein proteins, genetic mutations11 oxidative stress12 function13


, iron


, amyloid fibrils from ,


, and mutations affecting miRNA . They impact on neuronal damage in different


ways and in the majority of the cases the causes are not well known. Protein misfolding and aggregation is one of the


primary causes of AD, PD, HD, and prion disease, as well as other non-neurodegenerative diseases (e.g. cystic fibrosis)14


. Transcription turns DNA into RNA, and 48 ❚


translation of RNA results in protein. However, the often forgotten third step in this process, the folding of the translated linear strand of amino acids into a fully functional three-dimensional protein, is one of the most complex challenges facing the cellular protein factory15


. June 2012 | prime-journal.com


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