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Parkinson’ s Disease Casey Wang 12301016032

Parkinson’s Disease Casey Wang 12301016032

History In 1817, James Parkinson published An Essay of the Shaking Palsy Novel described six patients as having"Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellect being uninjured. Parkinson's Disease was known as paralysis agitans(shaking palsy in English), disease was later renamed by Jean-Marie Charcot ESSAY SHAKING PALSY CHAPTER L 物物 二一二≈

History • In 1817, James Parkinson published An Essay of the Shaking Palsy • Novel described six patients as having “Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellect being uninjured.” • Parkinson’s Disease was known as paralysis agitans(shaking palsy in English), disease was later renamed by Jean-Marie Charcot

What is Parkinson's disease? A progressive neurodegenerative disorder that affects movement Develops gradually, sometimes beginning with a tremor in just one PRR Repetitive "pill rolling hand. Stiffness or slowing of movement Parkinson 's disease cant be cured Persistent medications may improve symptoms. In later stages, surgery to regulate certain regions of the shuffling gait, taking brain may be suggested mall steps

What is Parkinson’s Disease? • A progressive neurodegenerative disorder that affects movement • Develops gradually, sometimes beginning with a tremor in just one hand. Stiffness, or slowing of movement • Parkinson's disease can't be cured, medications may improve symptoms. In later stages, surgery to regulate certain regions of the brain may be suggested

Who is affected? It is estimated that around 1 in 5oo people are affected by Parkinsons disease and there are currently 127,000 people in the UK with the condition Average age for symptoms to start is around 60; (1 in 20 cases first develop in people aged under 5o) Men are one-and-half times more likely to get Parkinsons disease than women Caucasians are at a higher risk Rates are significantly lower in african and Asian people

Who is affected? • It is estimated that around 1 in 500 people are affected by Parkinson’s disease and there are currently 127,000 people in the UK with the condition. • Average age for symptoms to start is around 60; (1 in 20 cases first develop in people aged under 50) • Men are one-and-half times more likely to get Parkinson’s disease than women. • Caucasians are at a higher risk. Rates are significantly lower in African and Asian people

symptoms Tremor. Shaking usually begins in the limbs. One characteristic of Parkinson's disease is tremor of your hand when it is relaxed (at rest) Slowed movement(bradykinesia) Occurs overtime, steps may become shorter when you walk, or find it difficult to get out of a chair, feet may stick to the floor as you try to walk making it difficult to move. Speech changes. Speech is soft, quick, slurred, and will hesitate before talking Monotone speech, without usual inflections Loss of automatic movements. Decreased ability to perform unconscious movements, including blinking, smiling Rigid muscles Impaired posture and balance Writing changes

Symptoms • Tremor. Shaking usually begins in the limbs. One characteristic of Parkinson's disease is tremor of your hand when it is relaxed (at rest). • Slowed movement (bradykinesia). Occurs overtime, steps may become shorter when you walk, or find it difficult to get out of a chair, feet may stick to the floor as you try to walk, making it difficult to move. • Speech changes. Speech is soft, quick, slurred, and will hesitate before talking. Monotone speech, without usual inflections • Loss of automatic movements. Decreased ability to perform unconscious movements, including blinking, smiling • Rigid muscles • Impaired posture and balance • Writing changes

Causes Parkinson's disease is caused by a loss of nerve cells in part of the substantia nigra, which leads to a reduction in the amount of a chemical called dopamine in the brain Dopamine plays a vital role in regulating the movement of the body and reduced dopamine level is responsible for many of the symptoms The cause behind loss of nerve cells is unclear most experts think it is due to a combination of genetic and environmental factors Diminished substantia nigra as seen in Parkinsons disease

Causes • Parkinson’s disease is caused by a loss of nerve cells in part of the substantia nigra, which leads to a reduction in the amount of a chemical called dopamine in the brain. • Dopamine plays a vital role in regulating the movement of the body and reduced dopamine level is responsible for many of the symptoms. • The cause behind loss of nerve cells is unclear. Most experts think it is due to a combination of genetic and environmental factors

Changes in the brain The presence of Lewy bodies. Clumps of specific substances within brain cells are microscopic markers A Lewy body, pictured above, contains a mass of proteins, including synuclein, of Pd. researchers believe these and is a characteristic feature of Parkinson's disease neural tissue Lewy bodies hold an important clue to the cause of parkinson's disease Normal Alpha-synuclein is found within Lewy bodies. An important natural and widespread protein among arkinson many It's found in all Lewy bodies in Pre a clumped form that cells can't break down

Changes in the Brain • The presence of Lewy bodies. Clumps of specific substances within brain cells are microscopic markers of PD. Researchers believe these Lewy bodies hold an important clue to the cause of Parkinson's disease. • Alpha-synuclein is found within Lewy bodies. An important natural and widespread protein among many. It's found in all Lewy bodies in a clumped form that cells can't break down

Associated Pd genes Alpha-synuclein(SNCA)-located on chromosome 4 is a specific gene that causes PD. Normally, the chromosome carries only a single copy of the alpha-synuclein gene lowa kindred'or Spellman-Muenter kindred, carried 3 copies of the gene Other mutated genes known to cause PD: parkin, leucine-rich repeat kinase 2, PTEN-induced putative kinase LRRK2-encodes for the protein, Dardarin -is only associated with PD. Mutations in the lrrK2 gene that lead to pd are most common in people of North African, Basque, Portuguese Some with LRRK2 mutations develop PD in their 30s-4oS, while others develop the disease in their 8os, and others never develop PD at all. People with LRRK2 gene mutations develop dementia, while others develop a form of Parkinsons that shares features with amyotrophic lateral sclerosis(ALS)

Associated PD Genes • Alpha-synuclein (SNCA) – located on chromosome 4 is a specific gene that causes PD. Normally, the chromosome carries only a single copy of the alpha-synuclein gene – ‘Iowa kindred’ or ‘Spellman-Muenter kindred,’ carried 3 copies of the gene. • Other mutated genes known to cause PD: parkin, leucine-rich repeat kinase 2, PTEN-induced putative kinase 1 • LRRK2 — encodes for the protein, Dardarin — is only associated with PD. Mutations in the LRRK2 gene that lead to PD are most common in people of North African, Basque, Portuguese – Some with LRRK2 mutations develop PD in their 30s-40s, while others develop the disease in their 80s, and others never develop PD at all. People with LRRK2 gene mutations develop dementia, while others develop a form of Parkinson’s that shares features with amyotrophic lateral sclerosis (ALS)

Research Mitochondrial dysfunction induced by knockdown of mortalin is rescued by parkin Animal Models: neurotoxin 6-hydroxydopamine, also known as 6 OHDA, creates a model of Parkinson's disease in rats by targeting and destroying dopaminergic neurons in the nigrostriatal pathway when injected into the substantia nigra Neuroprotective treatments: a vaccine that primes the human immune system to destroy alpha-synuclein, PDola(developed by Austrian company, Affiris), has entered clinical trials in humans

Research • Mitochondrial dysfunction induced by knockdown of mortalin is rescued by Parkin • Animal Models: neurotoxin 6-hydroxydopamine, also known as 6- OHDA, creates a model of Parkinson’s disease in rats by targeting and destroying dopaminergic neurons in the nigrostriatal pathway when injected into the substantia nigra • Neuroprotective treatments: A vaccine that primes the human immune system to destroy alpha-synuclein, PD01A (developed by Austrian company, Affiris), has entered clinical trials in humans

Contents lists available at Science Direct B Biochemical and Biophysical Research Communications B EI SEVIER journalhomepagewww.elsevier.com/locate/ybbre Mitochondrial dysfunction induced by knockdown of mortalin is rescued by Parkin Hui Yang. 1, Xiaoping Zhou. 1, Xiaoyu Liu Ling Yang, Qiang Chen Dongliang Zhao, Ji Zuo, Wen Lit Deparment of Celluar and Gentic Medrine, Shanghai Medcal Collge Furlan Universy, Shangha 200032. FR ine DEpartment of Neurolog. Agitated Prop Hospital Jiang Universiry, Zhenjiang 2120m. jiangsu Province. PR China ARTICLE INFO A BSTRACT Ande history Mutations in the parkin gene are the most common cause of autosomal recessive Parkinsons disease(PD). Received 7 May 2011 As an B3-ubiquitin ligase. Parkin is assodated with mitochondnal dynamics and mitophagy. Mortalin, a Available online 26 May 2011 olecular chaperone, is located primarily in mitochondria, where it functions to maintain mitochondnal