Dissertation work ppt
- 1. MANDARA V M 1ST YR., II SEM MSC BIOCHEMISTRY MAHARANI’S SCIENCE COLLEGE FOR WOMEN MYSURU Dissertation work on Parkinson’s disease
- 2. • Introduction. • History. • classification. • Causes. • Etiology. • Pathophysiology. • Biochemical aspects. • Signs and symptoms. • Diagnosis. • Treatment. • Prevention. • Epidemiology. Contents
- 3. • Parkinson's disease (PD) is a degenerative disorder of the central nervous system mainly affecting the motor system. • Mainly affecting the deep parts of brain cells which are involved in synthesising dopamine. • Dopamine- responsible for a circuit messages involved in coordinate normal movement. • In the absence it affects the striatum ( dopamine receptor) and it is not stimulated. • Thus it results in impartment of movement with tremor, slowness, stiffness or balance problem and other symptoms. • Along with the loss of dopamine it is also results from accumulation of Lewy bodies in the neurons. INTRODUCTION:
- 4. • The Parkinson’s disease is a condition that has been known about since ancient times. – Kampavata. • And its history expands from 1817 when James Parkinson published “An Essay on the Shaking Palsy”. • The term "Parkinson's disease" was coined several decades later by French neurologist Jean-Martin Charcot. • Early descriptions: • 10th century- An Ayurvedic medical treatment arise. • 12th century - Egyptian papyrus mentions a king drooling with age and the Bible contains a number of references to tremor • Galen wrote about a disease that almost certainly was PD, describing tremors that occur only at rest, postural changes and paralysis. • John Hunter - "paralysis agitans“ • Finally, Auguste François Chomel - several descriptions of abnormal movements and rigidity History: A Photograph of the book “An Essay on the shaking palsy” and its first page by James Parkinson
- 5. • 19th century : • James Parkinson - In 1817, James Parkinson published his essay reporting 6 cases of paralysis agitans. • later - Trousseau, Gowers, Kinnier Wilson and Erb, and most notably Jean Martin Charcot, made further additions to the knowledge of the disease. • 20th century and beyond: • Édouard Brissaud - proposed that it had its origin in the subthalamus or cerebral peduncle and might be caused by an ischemic lesion. • Frederic Lewy - In 1912, described a pathologic finding in affected brains, later named "Lewy bodies". • Arvid Carlsson – in 1950, biochemical changes in the brain identified, by the large work on the neurotransmitter He is eventually awarded a Nobel Prize for this work. • History of treatments: • Casimir Funk – in 1911, introduced levodopa • Alim-Louis Benabid and colleagues – in 1980, at Grenoble, France, introduced deep brain stimulation.
- 6. • Parkinson’s disease is the most common form of Parkinsonism and the term Parkinsonism is used for a motor syndrome whose main symptoms are tremor at rest, stiffness, slowing of movement and postural instability. • Parkinsonian syndromes can be divided into four subtypes, according to their origin: • Primary or idiopathic Parkinson’s disease – or simply Parkinson disease, caused due to dementia with Lewy bodies and Lewy neurites • Secondary or acquired Parkinsonism – group disorders, caused due to the use of antipsychotics. • Hereditary Parkinsonism – inherited i.e. some people may have genes that increase the possibility of developing Parkinson's. • Parkinson plus syndromes or multiple system degeneration - is a group of neurodegenerative diseases featuring the classical features of Parkinson's disease Classification : Lewy neurites LNs The Lewy bodies LBs
- 7. • Parkinson's disease in most people is idiopathic. • a small proportion of cases can be attributed to known genetic factors and environmental factors. • ETIOLOGY: • Environmental factors affecting PD • Heavy metals – originate from long-term exposure of the central nervous system to environmental chemicals. • Manganese, Aluminium, Iron, copper. • Pesticides exposure - pesticide exposure is associated with an increased risk for developing Parkinson’s disease. • Organochlorine class of pesticides, Rotenone, Paraquat. • Genetic factors affecting PD • 𝛼- synuclein • Parkin • Ubiquitin C terminal hydrolase- L1 • DJ-1 Causes:
- 8. • PATHOPHYSIOLOGY: • The pathologic hallmark of PD is degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), resulting in depletion of striatal dopamine. • nigrostriatal pathway. • It is composed of dopaminergic neurons whose cell bodies are located in the substantia nigra compacta. • These neurons project to the ganglia and synapse in the striatum.
- 9. • BIOCHEMICAL ASPECTS : • PD occurs due to degeneration of substantia nigra pars compacta dopaminergic • This results in decrease in dopamine content in nigra and striatum and this causes bradykinesia and rigidity • striatum contains D1 and D2 receptors • Dopamine is excitatory in D1 inhibitory in D2 receptor • Deficiency of dopamine at these receptors causes alteration in downstream nuclei
- 10. • There are four cardinal features of PD. • TRAP: Tremor at rest, Rigidity, Akinesia (or bradykinesia) and Postural instability. • Non motor symptoms include – • autonomic dysfunction, • cognitive/neurobehavioral disorders, • sensory and sleep abnormalities. Signs and symptoms:
- 11. • Accurate diagnosis of PD relies on clinical examination and a thorough review of a patient’s history. • No definitive laboratory or imaging tests are available to confirm the diagnosis until post-mortem. • There is a high error rate in the diagnosis. • Some of the diagnosing techniques are • Levodopa challenge – improved response to levodopa. • Imaging – SPECT measure of the uptake of micro labelled dopamine transporter protein. • Genetic testing – specific genes associated to PD were identified. • Olfactory testing – impartment of sense of smell. • Differential diagnosis – differentiating PD from other Parkinsonian syndromes. Diagnosis:
- 12. • While there is currently no cure for PD there are a range of treatment which can help in the management of the symptoms. • Available treatments include - range of prescription medications, surgery and physical and supportive therapies. • And this treatments are classified as • Symptomatic therapy – usually this involves medical prescriptions like levodopa, MAO-B inhibitors, Dopamine agonists and anticholinergic agents. • Neuroprotective therapy – these have modifying effects on disease, usually slow down the disease • this include MAO-B inhibitors like selegiline and Rasagiline • Surgical therapy - For patients who have motor fluctuations and dyskinesias surgery is considered. • And it includes deep brain stimulation and neuroablative lesion surgeries. Treatment :
- 13. • Gene therapy - Several studies have demonstrated the safety of gene therapy as a treatment for Parkinson disease
- 14. • There is no known way to prevent Parkinson's disease. • Research has shown that people who eat more fruits and vegetables, high-fiber foods, fish, and omega-3 rich oils and who eat less red meat and dairy may have some protection against Parkinson's. • Consuming high level - • omega-3 fats, Vitamin D, magnesium. • Reducing homocysteine level in food and also reducing toxic load or exposure. Prevention :
- 15. • Parkinson disease is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. • The incidence and prevalence of Parkinson disease increase with age. • Parkinson disease is about 1.5 times more common in men than in women. Epidemiology:
- 16. • Parkinson’s disease results from a gradual loss of neurons that produce dopamine. • This causes an imbalance in the brain leading to symptoms of tremor, gait problems and cognitive decline. • The histological pathogenesis of this disorder is known, but the cause of the loss of dopaminergic cells in the substantia nigra is not clear. • It seems likely that the disorder has several, multifactorial causes in different groups of patients. • Diagnosis is made on clinical grounds and treatment is typically through oral medication intended to replace dopamine. • More radical therapies such as deep brain stimulation and surgical lesioning are explored. • Continued scientific research into Parkinson’s disease may reveal important clues to help find more effective treatments in the future. Conclusion :