One STEP Closer to Curing Alzheimer's Disease. Animation by The Art of the Cell

Dr. Paul Lombroso, researcher at Yale University's Laboratory of Molecular Neuroscience is investigating a small molecule that is capable of inhibiting a protein involved in the development and progression of Alzheimer's disease (AD).

He first discovered this protein, called STEP, about 20 years ago here at Yale. His lab's recent work shows that the brains of humans and mouse models with AD have too much of this STEP protein.

They now know that the increases in STEP protein levels contribute to the cognitive problems associated with AD. They were excited to find that learning and memory actually improves after decreasing STEP activity in a mouse model of AD, and they now have a small molecule that inhibits STEP. This small molecule forms the basis of this project because it may some day be used to treat AD.

This campaign has three clear-cut goals:

1. Test new drugs based on the STEP inhibitor that they have in the lab to find more potent ones.

2. Chemically modify these drugs so they can be easily taken by mouth.

3. Test the new compounds in other animals with cognitive deficits. At the end of this campaign, Paul and his team will be closer to their overarching goal of bringing a novel therapeutic drug to human clinical trials to treat this devastating disease.

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Art of the Cell - is a Connecticut-based Medical and Scientific 3D Animation company led by award-winning 3D artist and illustrator, John Liebler.

John Liebler, former Lead Medical Animator for XVIVO Scientific Animation, is best known for working with Harvard Biovisions to create their pivotal molecular animation "The Inner Life of the Cell". He has over 20 years of experience creating art for education. Today he uses 3D computer animation to create scientific images and animations for a wide range of pharmaceutical, biotech, and educational organizations. From science animation videos used to explain cell biology to students, to scientific method animations used to explain the research of pioneers in the field of bio-science, John's biomedical animations have been used educate and inspire audiences on all levels.

John and his team are able to present complex medical and scientific information in moving images that balance scientific accuracy with accessible storytelling and a strong focus on visual appeal.

[khelms]

Looked like an endocannabinoid (step inhibitor)

After glutamate signaling via mglutR triggers calcium in and potassium out, post synaptic calcium influx creates ecb production and retrograde inhibitory aka hyper polarizing transmission via presynaptic cb1activity (cb1 is a pro homeostatic antiexcitotoxic GPCR very potent on glutamatergic neurons) (moa mechanism of action: DISE, depolarization induced suppression of excitation) thus fixing the problem upstream of STEP (overexcitation)


So your answer is restoring homeostatic pathways such as the ECS, endocannabinoid system

Hypothesis: ECS exhaustion is directly related to over expression of step