A Correlation Between Alzheimer’s and Parkinson’s: Inflammatory

Response to Endogenous Neuro-protective Mechanisms

Peter H. Massey

“Brain Attacks”α CVDs are the principal cause of death in Western civilizations,

accounting for more than 40% of all deaths.

α Cerebrovascular Disease – disease of blood vessels supplying the brain

- Sustained hypertension - narrow, stiff, deformed

α Stroke – loss of blood supply – leads to paralysis

α Aneurysm – blood filled dilation of blood vessel – if ruptured extremely harmful

α Ischemia – temporary paralysis

http://medicalimages.allrefer.com/large/stroke.jpg

Protein Activationα Basal ganglia

- dopamine & acetylcholine - transmission of nerve impulses

http://stemcells.nih.gov/StaticResources/info/scireport/images/figure82.jpg

http://www.nature.com/nrn/journal/v2/n7/images/nrn0701_492a_f2.gif

Parkinson’s Basics

http://www.mitosciences.com/images/parkinsons.jpg

http://www.about-dementia.com/articles/images/ParkinsonsDopamine.jpg

α Parkinson's disease - between the ages of 50 and 65 - 1% of the population

Symptoms

Parkinson’s

α Slowness of voluntary movements, especially in the initiation of such movements as walking or rolling over in bedα Decreased facial expression, monotonous speech, and decreased eye blinkingα A shuffling gait with poor arm swing and stooped postureα Unsteady balance; difficulty rising from a sitting positionα Continuous "pill-rolling" motion of the thumb and forefingerα Abnormal tone or stiffness in the trunk and extremitiesα Swallowing problems in later stages

Alzheimer’s

α Dementia: both long term and short term in later stages of life

α Loss of reasoning & logic

Parkinson’s Linked to Alzheimer’s

α Alpha-synuclein - accumulate into Lewy bodies inside nerve cells

- found in the amyloid plaques in Alzheimer's disease

α Alpha-synuclein - binds to membranes on nerve cells – lipids

(Deniz, March 2009 - PNAS)

http://len.epfl.ch/webdav/site/len/shared/import/migration/parki1_1.jpg

Inflammatory Response

α Inflammation - response to infection or injury- Damaged tissue releases chemicals - attract

white blood cells - Cytokines - accelerate inflammation

http://lpi.oregonstate.edu/ss03/lipoicacid.html

Inflammatory Response (continued)

α Inflammatory cytokines - stimulate production of adhesion molecules

- adhesion molecules prone to atherosclerosis- important target for treatment of atherosclerosis & CVD

α Inflammatory molecules - recruitment of white blood cells into the blood vessel wall - abnormal foam cells & atherosclerotic lesions

α Alpha-lipoic acid - ‘metal chelators’- inhibit white blood cell recruitment - preventing infection and inflammation - reducing oxidative stress - bolstering antioxidant defenses

http://www.nature.com/nrn/journal/v7/n1/images/nrn1829-f3.jpg

Inflammation Linked to Parkinson’sα Nurr1 - transcription factor

α Nurr1 protein - microglia & astrocytes- Microglia are macrophage-like cells - immune defense in

the central nervous system- Astrocytes - large star-shaped support functions (keep cell

alive)

α Absense of Nurr1 - inflammation increased - toxic effect on those neurons

University of California - San Diego (2009, April 6). Protein Protects Neurons In Brain From Damage Due To Inflammation. ScienceDaily.

Observing Brain Activity

α Brain Culture – advantageous – one specimen over prolonged period

α Fluorescence microscopy

α Induced axonal damage

α Inflammatory response initiated

α Axonal regeneration observed

http://www.neuro-zone.com/writable/content_attachments/neurons%20in%20network.jpg

http://www.amicusvisualsolutions.com/obrasky/06015_02W.jpg

Treatment

α Balance of the neurotransmitters acetylcholine & dopamine

α Success with experiments involving operative procedures - too invasive

http://www.herbsandtinctures.co.uk/images/maca-capsules.jpg

α-Lipoic Acid

α Anti-inflammatory: cell signaling processes; sensitivity, metabolism, and stress response

α Inflammation & cell cycle control

α Reproduces endogenous anti-oxidants: glutathione, vitamin C and E

α Removes superoxide anions, hydroxyl radicals, and other toxic ROS from body (the cell)

α Both hippocamal regions and basal ganglia (hydrophilic & hydrophobic)

α Related to inflammation & oxidative stress

http://aging-management.com/images/Lipoic-acid-2D-skeletal.png

Sepsis

Hotchkiss and Nicholson Nature Reviews Immunology advance online publication;published online 13 October 2006 | doi:10.1038/nri1943

Sepsis-associated Encephalopathy

α Feinstein Institute for Medical Research Dr. Sangeeta Chavan - sepsisDr. Kevin Tracey – Vagus nerve stimulation block

inflammatory response leading to disease (sepsis)

α Encephalopathy – infection of blood – brain dysfunction (may be due to direct infection of spinal cord)

- Sepsis – whole body inflammatory state

http://focosi.altervista.org/sepsis.jpg

Selected ReferencesBaier, Anne DeLotto. “In Earl Diagnosis of Alzheimer’s Disease, MRI Brain Scans Accurate.” Medical News Today. 25 December, 2008.

Bier, Ethan. “Antioxidants put Parkinson flies back in the PINK.” The National Academy of Science of the USA. 2006.

Clark et al. “Mitochindria, flies, and Parkinson’s disease.” Nature, 441, 1162-1166. January 2009.

Dawson, Ted. “Protein Target for Parkinson's’ Disease.” Johns Hopkins’ Insittute for Cell Engineering. 2 Dec, 2005.

DeLegge, Mark H. “Neurodegeneration and Inflammation.” Nutrition and Clinical Practice. Vol. 23, No. 1, 35-41. 2008.

Feany, M.B. “A Drosophila Model of Parkinson’s Disease,” Nature. 404, 394-398. March 23, 2000.

Georgetown University Medical Center (2008, September 11). “How Parkinson’s Develops: Protein Found That Regulated Gene Critical to Dopamine-releasing Brain Cells.” Science Daily.

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Northwestern University (2006, January 19). “Gene Tharpy ‘Turns Off’ Mutation Linked to Parkinson’s Disease. Science Daily.

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University of California (2009, April 6). “Protein Protects Neurons in Brain From Damage Due to Inflammation.” Science Daily.

Weiss, R. “Human Brain Neurons Grown in Culture.” Science News. May 5, 1990.

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