DISEASES CAUSED BY PROTEIN DAMAGEBy: Abenezer Abraham

3 Diseases -Parkinson’s Disease

-Lou Gehrig’s Disease

Alzheimer’s Disease

Parkinson’s Disease

Parkinson’s Disease

2 Steps & 2 enzymes

1st Step and 1st Enzyme 1st Step -L-tyrosine + THFA +O2 + Fe2+ L-dopa

+ DHFA + H20 + Fe2+

Enzyme: Tyrosine-3-Monooxygenase

2nd Step and 2nd Enzyme 2nd Step L-dopa + pyridoxal

phosphateDopamine +pyridoxal phosphate + CO2

Enzyme: Dopa Carboxylase

Parkinson’s Treatment

Lou Gehrig’s Disease (ALS)

Lou Gehrig’s Disease (ALS)

TDP-43 Protein

TDP-43 (Location, Location,Location) -Normally located in the Nucleus

-Involved in regulating DNA translation into RNA and transcription of RNA to proteins.

-However…

Alzheimer’s Disease

Two Hypotheses Amyloid Cascade Hypothesis

-Neuronal Cytoskeletal Degeneration Hypothesis

Amyloid Cascade Hypothesis-Abnormal processing of the amyloid

precursor protein leads to a series of events that result in Alzheimer’s.

-Beta Amyloid Plaques

Neuronal Cytoskeletal Degeneration Hypothesis

-Proposes that cytoskeletal problems are the main cause of Alzheimer’s.

-Tau Proteins

Tau Proteins -Aid in regulating Microtubule

construction

-Also interact with Actin filaments

-Hyperphosphorylation

Tau Proteins

Beta Amyloid Plaques

Amyloid Precursor Protein Cleavage (APP)

-Involves 3 Enzymes

-Beta, Alpha, and Gamma Secretase enzymes

3 Enzymes -The Beta Secretase produces CT99

Alpha Secretase The Alpha Secretase produces CT83

Gamma SecretaseThe Gamma Secretase forms Beta Amyloid 40 (Major) and the Beta Amyloid 42 (minor)

*The Beta Amyloid 42 forms amyloid plaque

The Problem -Mutations near the Beta and Gamma

Secretase cleavage sites result in increased production of Beta Amyloid 42 which results in increased Amount of plaques surrounding the neuron

There’s Still Work to Be Done -While there is much that is yet to be

understood about the exact details of the damage done to this proteins, much research is still being done to ultimately prevent these diseases.