Target- and mechanism-based therapeutics for neurodegenerative diseases: Strength in numbers

Paul C. Trippier, Kristin Jansen Labby, Dustin D. Hawker, Jan J. Mataka, Richard B. Silverman

Research output: Contribution to journalReview article

81 Citations (Scopus)

Abstract

The development of new therapeutics for the treatment of neurodegenerative pathophysiologies currently stands at a crossroads. This presents an opportunity to transition future drug discovery efforts to target disease modification, an area in which much still remains unknown. In this Perspective we examine recent progress in the areas of neurodegenerative drug discovery, focusing on some of the most common targets and mechanisms: N-methyl-d-aspartic acid (NMDA) receptors, voltage gated calcium channels (VGCCs), neuronal nitric oxide synthase (nNOS), oxidative stress from reactive oxygen species, and protein aggregation. These represent the key players identified in neurodegeneration and are part of a complex, intertwined signaling cascade. The synergistic delivery of two or more compounds directed against these targets, along with the design of small molecules with multiple modes of action, should be explored in pursuit of more effective clinical treatments for neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)3121-3147
Number of pages27
JournalJournal of Medicinal Chemistry
Volume56
Issue number8
DOIs
StatePublished - Apr 25 2013

Fingerprint

Drug Discovery
Neurodegenerative Diseases
Nitric Oxide Synthase Type I
Calcium Channels
Reactive Oxygen Species
Oxidative Stress
Therapeutics
Proteins
aspartic acid receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Target- and mechanism-based therapeutics for neurodegenerative diseases : Strength in numbers. / Trippier, Paul C.; Jansen Labby, Kristin; Hawker, Dustin D.; Mataka, Jan J.; Silverman, Richard B.

In: Journal of Medicinal Chemistry, Vol. 56, No. 8, 25.04.2013, p. 3121-3147.

Research output: Contribution to journalReview article

Trippier, Paul C. ; Jansen Labby, Kristin ; Hawker, Dustin D. ; Mataka, Jan J. ; Silverman, Richard B. / Target- and mechanism-based therapeutics for neurodegenerative diseases : Strength in numbers. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 8. pp. 3121-3147.
@article{0b77da71fcdd45d8b8b8868aed503300,
title = "Target- and mechanism-based therapeutics for neurodegenerative diseases: Strength in numbers",
abstract = "The development of new therapeutics for the treatment of neurodegenerative pathophysiologies currently stands at a crossroads. This presents an opportunity to transition future drug discovery efforts to target disease modification, an area in which much still remains unknown. In this Perspective we examine recent progress in the areas of neurodegenerative drug discovery, focusing on some of the most common targets and mechanisms: N-methyl-d-aspartic acid (NMDA) receptors, voltage gated calcium channels (VGCCs), neuronal nitric oxide synthase (nNOS), oxidative stress from reactive oxygen species, and protein aggregation. These represent the key players identified in neurodegeneration and are part of a complex, intertwined signaling cascade. The synergistic delivery of two or more compounds directed against these targets, along with the design of small molecules with multiple modes of action, should be explored in pursuit of more effective clinical treatments for neurodegenerative diseases.",
author = "Trippier, {Paul C.} and {Jansen Labby}, Kristin and Hawker, {Dustin D.} and Mataka, {Jan J.} and Silverman, {Richard B.}",
year = "2013",
month = "4",
day = "25",
doi = "10.1021/jm3015926",
language = "English (US)",
volume = "56",
pages = "3121--3147",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Target- and mechanism-based therapeutics for neurodegenerative diseases

T2 - Strength in numbers

AU - Trippier, Paul C.

AU - Jansen Labby, Kristin

AU - Hawker, Dustin D.

AU - Mataka, Jan J.

AU - Silverman, Richard B.

PY - 2013/4/25

Y1 - 2013/4/25

N2 - The development of new therapeutics for the treatment of neurodegenerative pathophysiologies currently stands at a crossroads. This presents an opportunity to transition future drug discovery efforts to target disease modification, an area in which much still remains unknown. In this Perspective we examine recent progress in the areas of neurodegenerative drug discovery, focusing on some of the most common targets and mechanisms: N-methyl-d-aspartic acid (NMDA) receptors, voltage gated calcium channels (VGCCs), neuronal nitric oxide synthase (nNOS), oxidative stress from reactive oxygen species, and protein aggregation. These represent the key players identified in neurodegeneration and are part of a complex, intertwined signaling cascade. The synergistic delivery of two or more compounds directed against these targets, along with the design of small molecules with multiple modes of action, should be explored in pursuit of more effective clinical treatments for neurodegenerative diseases.

AB - The development of new therapeutics for the treatment of neurodegenerative pathophysiologies currently stands at a crossroads. This presents an opportunity to transition future drug discovery efforts to target disease modification, an area in which much still remains unknown. In this Perspective we examine recent progress in the areas of neurodegenerative drug discovery, focusing on some of the most common targets and mechanisms: N-methyl-d-aspartic acid (NMDA) receptors, voltage gated calcium channels (VGCCs), neuronal nitric oxide synthase (nNOS), oxidative stress from reactive oxygen species, and protein aggregation. These represent the key players identified in neurodegeneration and are part of a complex, intertwined signaling cascade. The synergistic delivery of two or more compounds directed against these targets, along with the design of small molecules with multiple modes of action, should be explored in pursuit of more effective clinical treatments for neurodegenerative diseases.

UR - http://www.scopus.com/inward/record.url?scp=84876832340&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876832340&partnerID=8YFLogxK

U2 - 10.1021/jm3015926

DO - 10.1021/jm3015926

M3 - Review article

C2 - 23458846

AN - SCOPUS:84876832340

VL - 56

SP - 3121

EP - 3147

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 8

ER -