Pathologically activated therapeutics for neuroprotection

@article{Lipton2007PathologicallyAT,
  title={Pathologically activated therapeutics for neuroprotection},
  author={Stuart A. Lipton},
  journal={Nature Reviews Neuroscience},
  year={2007},
  volume={8},
  pages={803-808}
}
  • S. Lipton
  • Published 1 October 2007
  • Biology, Psychology
  • Nature Reviews Neuroscience
Many drugs that have been developed to treat neurodegenerative diseases fail to gain approval for clinical use because they are not well tolerated in humans. In this article, I describe a series of strategies for the development of neuroprotective therapeutics that are both effective and well tolerated. These strategies are based on the principle that drugs should be activated by the pathological state that they are intended to inhibit. This approach has already met with success, and has led to… 

Figures from this paper

Pathologically activated therapeutics for neuroprotection
  • S. Lipton
  • Biology, Psychology
    Nature Reviews Neuroscience
  • 2007
TLDR
This article describes a series of strategies for the development of neuroprotective therapeutics that are both effective and well tolerated, based on the principle that drugs should be activated by the pathological state that they are intended to inhibit.
Receptor abuse-dependent antagonism for neuroprotection
  • H. Manev
  • Biology, Medicine
    Nature Reviews Neuroscience
  • 2007
TLDR
The neuroprotective PAT described in the Perspective article include RADA, a set of guidelines for designing neuroprot protective drugs capable of selectively blocking the pathological effects of the neurotransmitter glutamate in neurons surrounding ischemic/injured brain areas while leaving the physiological actions of glutamate in nonlesioned areas of the brain unaffected.
Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers.
TLDR
Recent progress in the areas of neurodegenerative drug discovery is examined, 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.
Therapeutic potential of mGluR5 targeting in Alzheimer's disease
TLDR
The potential of mGluR5, a metabotropic glutamatergic receptor, in understanding the mechanism underlying the neuronal death and neuroinflammation in AD is highlighted and the potential of this receptor as target for treating AD is discussed.
Ginsenoside Rd for acute ischemic stroke: translating from bench to bedside
TLDR
This article attempts to provide a synopsis of the physiochemical profile, pharmacokinetics, pharmacodynamics, clinical efficacy, safety and putative therapeutic mechanisms of Rd and discusses the validity of Rd as a neuroprotective agent for acute ischemic stroke.
Pharmacologically targeted NMDA receptor antagonism by NitroMemantine for cerebrovascular disease
TLDR
Novel NitroMemantines are described, comprising an adamantane moiety that binds in the NMDAR-associated ion channel that is used to target a nitro group to redox-mediated regulatory sites on the receptor and are both well tolerated and effective against cerebral infarction in rodent models.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 81 REFERENCES
Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond
  • S. Lipton
  • Biology
    Nature Reviews Drug Discovery
  • 2006
TLDR
The molecular basis for memantine efficacy in neurological diseases that are mediated, at least in part, by overactivation of NMDARs, producing excessive Ca2+ influx through the receptor's associated ion channel and consequent free-radical formation is reviewed.
NMDA receptor pathways as drug targets
TLDR
The future prospects for drugs that act on NMDA receptor pathways are critically assessed, including potential treatments for some major disorders such as stroke and Alzheimer's disease, for which effective therapies are still lacking.
The chemical biology of clinically tolerated NMDA receptor antagonists
Most neuroprotective drugs have failed in clinical trials because of side‐effects, causing normal brain function to become compromised. A case in point concerns antagonists of the
Emerging treatments for stroke in humans.
Pathways to neuronal injury and apoptosis in HIV-associated dementia
TLDR
Human immunodeficiency virus-1 (HIV-1) can induce dementia with alarming occurrence worldwide, but discovery in brain of HIV-1-binding sites (chemokine receptors) provides new insights.
Pathways towards and away from Alzheimer's disease
TLDR
Rapid progress towards understanding the cellular and molecular alterations that are responsible for the neuron's demise may soon help in developing effective preventative and therapeutic strategies in Alzheimer's disease.
Erythropoietin Therapy for Acute Stroke Is Both Safe and Beneficial
TLDR
Intravenous high-dose rhEPO is well tolerated in acute ischemic stroke and associated with an improvement in clinical outcome at 1 month, and analysis of covariance controlled for these two variables indicated thatrhEPO treatment was associated with a improvement in follow-up and outcome scales.
Emerging biological roles for erythropoietin in the nervous system
TLDR
In the third sentence of the first paragraph on page 490, the description of the human stroke study should have cited the following reference: Ehrenreich, H. et al.
...
1
2
3
4
5
...