L-DOPA

Summary

DISPLAYTITLE:L-DOPA -DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA, make it via biosynthesis from the amino acid -tyrosine. -DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, -DOPA itself mediates neurotrophic factor release by the brain and CNS. -DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia. -DOPA has a counterpart with opposite chirality, -DOPA. As is true for many molecules, the human body produces only one of the

Official source

https://en.wikipedia.org/wiki/L-DOPA

About this result

This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.

Related publications (9)

Related publications

Related people (1)

Related people

Related units

No results

Related units

Related concepts (45)

Related concepts

Related courses (7)

Related courses

Related lectures (13)

Related lectures

A Multiscale, Systems-Level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching Under Normal, Parkinsonian, and Levodopa Medication Conditions

Vignayanandam Ravindernath Muddapu

In order to understand the link between substantia nigra pars compacta (SNc) cell loss and Parkinson's disease (PD) symptoms, we developed a multiscale computational model that can replicate the symptoms at the behavioural level by incorporating the key cellular and molecular mechanisms underlying PD pathology. There is a modelling tradition that links dopamine to reward and uses reinforcement learning (RL) concepts to model the basal ganglia. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it in the RL-based behavioural model, which simulates the arm reaching task. Our results successfully replicated the impact of SNc cell loss and levodopa (L-DOPA) medication on reaching performance. It also shows the side effects of medication, such as wearing off and peak dosage dyskinesias. The model demonstrates how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD. It was able to predict the optimum L-DOPA medication dosage for varying degrees of cell loss. The proposed model has a potential clinical application where drug dosage can be optimised as per patient characteristics.

FRONTIERS MEDIA SA2022

Lipid membranes are complex and dynamic systems which are known to mediate signaling processes between cells and their environment. To do this multiple ion channels and pumps are involved in controlling the in- and out-flux of various ions (K+, Na+, Mg2+, Ca2+, etc.) and help maintain and regulate a concentration gradient of ions across the membrane. Additionally, membranes are semi-permeable for some species including water and even ions. However, molecular level information about passive and active transport of ions across lipid membranes is either missing or incomplete and ignores membrane hydration without which a membrane would not self-assemble.In this project, we use high-throughput wide-field second harmonic (SH) microscopy to learn about the molecular level structure of membrane interfaces during those processes by imaging the non-resonant response of interfacial water. We show that this technique is extremely sensitive to the transmembrane distribution of interfacial ions which disturb membrane hydration and thus change SH contrast. We apply this technique to probe the molecular structure(orientational order of water, strength of ion binding) at the interfaces of freestanding lipid bilayers and giant unilamellar vesicles (GUVs). We start with SH imaging of operational voltage-gated alamethicin ion channels in freestanding lipid membranes surrounded by an aqueous solution on either side. We observe a change in SH intensity upon channel activation that is traced back to a change in the orientational distribution of water molecules caused by transported ions. Of the transported ions, a fraction of 10-4 arrives at the hydrated membrane interface, leading to interfacial electrostatic changes on the time scale of a second. Later on, in order to improve SH contrast from low-emitting samples (such as interfacial water) and thus be able to study even more fundamental and delicate surface processes, we develop and build a femtosecond optical parametric amplifier. This laser system generates a tunable output in the range from 670 nm to 1000 nm at a 1 MHz repetition rate with a minimum pulse duration of 23 fs at 900 nm. Comparing our current femtosecond laser system with the new one at equal fluences we experimentally observe a 30 times improvement in SH contrast of low-emitting samples.Then, we present a new approach of label-free second harmonic imaging of GUV hydration which directly reports on the cross-membrane distribution of divalent cations bound to negatively charged lipid headgroups. We use this property to study passive transport of Ca2+ ions through lipid membranes. By varying the hydrophobic core of the bilayer, we observe Ca2+ translocation for mono-unsaturated (DOPC:DOPA) membranes which is reduced upon adding cholesterol. A complete inhibition of translocation is observed for branched (DPhPC:DPhPA) and poly-unsaturated (SLPC:SLPA) lipid membranes. In order to gain more insight into the mechanism of divalent cation transport, we perform a series of experiments with different ions (Mg2+, Ba2+, Ca2+and Cu2+). Surprisingly, we observe translocation of Ba2+, Ca2+ and Cu2+ ions through unsaturated DOPC:DOPA membranes which fully neutralize the inner membrane leaflet. Translocation time increases in the order Cu2+< Ca2+< Ba2+, while Mg2+ ions do not show any permeation. The observed trend in passive transport correlates with a trend in ion binding strength measured on impermeable GUVs with the same headgroup composition.

EPFL2021

The anti-Parkinsonian drug selegiline delays the nucleation phase of α-synuclein aggregation leading to the formation of nontoxic species

Saviana Di Giovanni, Hilal Lashuel

Parkinson's disease (PD) is a movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of intraneuronal inclusions called Lewy bodies, which are composed mainly of α-synuclein (α-syn). Selegiline (Sel) is a noncompetitive monoamino oxidase B inhibitor that has neuroprotective effects and has been administered to PD patients as monotherapy or in combination with l-dopa. Besides its known effect of increasing the level of dopamine (DA) by monoamino oxidase B inhibition, Sel induces other effects that contribute to its action against PD. We evaluated the effects of Sel on the in vitro aggregation of A30P and wild-type α-syn. Sel delays fibril formation by extending the lag phase of aggregation. In the presence of Sel, electron microscopy reveals amorphous heterogeneous aggregates, including large annular species, which are innocuous to a primary culture enriched in dopaminergic neurons, while their age-matched counterparts are toxic. The inhibitory effect displayed by Sel is abolished when seeds (small fibril pieces) are added to the aggregation reaction, reinforcing the hypothesis that Sel interferes with early nuclei formation and, to a lesser extent, with fibril elongation. NMR experiments indicate that Sel does not interact with monomeric α-syn. Interestingly, when added in combination with DA (which favors the formation of toxic protofibrils), Sel overrides the inhibitory effect of DA and favors fibrillation. Additionally, Sel blocks the formation of smaller toxic aggregates by perturbing DA-dependent fibril disaggregation. These effects might be beneficial for PD patients, since the sequestration of protofibrils into fibrils or the inhibition of fibril dissociation could alleviate the toxic effects of protofibrils on dopaminergic neurons. In nondopaminergic neurons, Sel might slow the fibrillation, giving rise to the formation of large nontoxic aggregates.

2010

The anti-Parkinsonian drug selegiline delays the nucleation phase of α-synuclein aggregation leading to the formation of nontoxic species

Saviana Di Giovanni, Hilal Lashuel

2010

EPFL2021