Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

164
Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
164
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists01:30

Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists

131
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
131
Alzheimer's Disease: Treatment01:22

Alzheimer's Disease: Treatment

200
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
200
Cognitive Development During Adulthood01:30

Cognitive Development During Adulthood

125
Cognitive development continues throughout adulthood, undergoing significant shifts across early, middle, and late stages. Individual transition occurs from adolescent idealism to pragmatic and adaptable thinking in early adulthood. During this period, individuals learn to integrate personal beliefs with the recognition that other perspectives are equally valid. Exposure to the complexities of modern society, diverse experiences, and higher education contribute to this adaptive thought process,...
125
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

192
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
192
Antihypertensive Drugs: Vasodilators01:23

Antihypertensive Drugs: Vasodilators

543
Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
543

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

CRISPR Gene Tagging for Illuminating Endogenous Protein Dynamics.

International journal of molecular sciences·2026
Same author

Rescuing the Function of Missense-Mutated Tumor Suppressor <i>VHL</i> using Stabilizing Small Molecules.

bioRxiv : the preprint server for biology·2026
Same author

Correction to "Potent, Selective Pyrrolopyrimidine PDE11A4 Inhibitors with Improved Pharmaceutical Properties".

ACS medicinal chemistry letters·2026
Same author

A fission yeast-based platform for nematode PDE inhibitor discovery.

Cellular signalling·2026
Same author

P2X7R-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics.

Brain : a journal of neurology·2026
Same author

Potent, Selective Pyrrolopyrimidine PDE11A4 Inhibitors with Improved Pharmaceutical Properties.

ACS medicinal chemistry letters·2026

Related Experiment Video

Updated: Jul 12, 2025

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment
12:18

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment

Published on: January 11, 2020

7.6K

First Optimization of Novel, Potent, Selective PDE11A4 Inhibitors for Age-Related Cognitive Decline.

Shams Ul Mahmood1,2, Mariana Lozano Gonzalez1,2, Sreedhar Tummalapalli1,2

  • 1Department of Chemistry & Biochemistry, Montclair State University, Montclair, New Jersey 07043, United States.

Journal of Medicinal Chemistry
|October 20, 2023
PubMed
Summary

Inhibiting phosphodiesterase 11A4 (PDE11A4), found in the memory-forming hippocampus, may combat age-related cognitive decline. PDE11A4 inhibitors show promise for treating memory deficits in aging.

More Related Videos

Highlighting and Reducing the Impact of Negative Aging Stereotypes During Older Adults' Cognitive Testing
06:58

Highlighting and Reducing the Impact of Negative Aging Stereotypes During Older Adults' Cognitive Testing

Published on: January 24, 2020

7.4K
Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach
10:13

Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach

Published on: February 14, 2014

13.7K

Related Experiment Videos

Last Updated: Jul 12, 2025

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment
12:18

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment

Published on: January 11, 2020

7.6K
Highlighting and Reducing the Impact of Negative Aging Stereotypes During Older Adults' Cognitive Testing
06:58

Highlighting and Reducing the Impact of Negative Aging Stereotypes During Older Adults' Cognitive Testing

Published on: January 24, 2020

7.4K
Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach
10:13

Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach

Published on: February 14, 2014

13.7K

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Phosphodiesterase 11A4 (PDE11A4) is a cyclic nucleotide hydrolase uniquely expressed in the hippocampal formation, crucial for long-term memory.
  • PDE11A4 expression elevates in the aging hippocampus in both humans and rodents.
  • PDE11A knockout mice exhibit no age-related memory deficits or histopathology.

Purpose of the Study:

  • To develop potent and selective PDE11A4 inhibitors for potential therapeutic use.
  • To investigate the therapeutic potential of PDE11A4 inhibition for age-related cognitive decline.

Main Methods:

  • Utilized a yeast-based high-throughput screen to identify initial PDE11A4 inhibitors.
  • Optimized lead compounds to enhance potency and pharmaceutical properties.
  • Assessed inhibitor potency and selectivity in cell-based assays.

Main Results:

  • Achieved a greater than 10-fold increase in inhibitor potency.
  • Developed selective, cell-penetrant PDE11A4 inhibitors.
  • Identified an inhibitor 10-fold more potent than tadalafil in cell-based activity.

Conclusions:

  • PDE11A4 inhibition represents a viable therapeutic strategy for age-related memory decline.
  • Optimized PDE11A4 inhibitors demonstrate significant potency and cell permeability.