Benzofuran Iboga-analogs Modulate Nociception and Inflammation in an Acute Mouse Pain Model.

Pain management following acute injury or post-operative procedures is highly necessary for proper recovery and quality of life. Opioids and non-steroidal anti-inflammatory drugs (NSAIDS) have been used for this purpose, but opioids cause addiction and withdrawal symptoms whereas NSAIDS have several systemic toxicities. Derivatives of the naturally occurring iboga alkaloids have previously shown promising behavior in anti-addiction of morphine by virtue of their interaction with opioid receptors. On this frontier, four benzofuran analogs of the iboga family have been synthesized and their analgesic effects have been studied in formalin induced acute pain model in Swiss albino mice at 30 mg/kg of body weight dose administered intraperitoneally. The antioxidant, anti-inflammatory and neuro-modulatory effects of the analogs were analyzed. Reversal of tail flick latency, restricted locomotion and anxiogenic behavior were observed in iboga alcohol, primary amide and secondary amide. Local neuroinflammatory mediators' substance P, calcitonin gene related peptide, cyclooxygenase-2 and p65 were significantly decreased whereas the depletion of brain derived neurotrophic factor and glia derived neurotrophic factor was overturned on iboga analog treatment. Behavioral patterns after oral administration of the best analog were also analyzed. Taken together, these results show that the iboga family of alkaloid has huge potential in pain management.

Levodopa-induced Dyskinesia in Parkinson's Disease: Plausible Inflammatory and Oxidative Stress Biomarkers.

BACKGROUND: Pathophysiology of levodopa-induced dyskinesia (LID) remains obscure. Increased dopamine metabolism due to prolonged levodopa treatment can exacerbate oxidative damage and neuroinflammatory pathology in Parkinson's disease (PD). Association of novel peripheral markers with LID severity might provide insight into LID pathomechanisms. OBJECTIVE: We aimed to study specific peripheral blood inflammatory-oxidative markers in LID patients and investigate their association with clinical severity of LID. METHOD: Motor, non-motor and cognitive changes in PD with and without LID compared to healthy-matched controls were identified. Within the same cohort, inflammatory marker (sLAG3, TOLLIP, NLRP3 and IL-1ß) levels and antioxidant enzyme activities were determined by ELISA and spectrophotometric methods. RESULTS: LID patients showed distinctly upregulated TOLLIP, IL-1ß levels with significant diminution of antioxidant activity compared to controls. Significant negative association of cognitive markers with oxidative changes was also observed. CONCLUSION: To our understanding, this is the first study that indicates the involvement of toll-like receptor-mediated distinct and low-grade inflammatory activation in LID pathophysiology.

Design of Chiral ß-Double Helices from γ-Peptide Foldamers.

Chirality is ubiquitous in nature, and homochirality is manifested in many biomolecules. Although ß-double helices are rare in peptides and proteins, they consist of alternating L- and D-amino acids. No peptide double helices with homochiral amino acids have been observed. Here, we report chiral ß-double helices constructed from γ-peptides consisting of alternating achiral (E)-α,ß-unsaturated 4,4-dimethyl γ-amino acids and chiral (E)-α,ß-unsaturated γ-amino acids in both single crystals and in solution. The two independent strands of the same peptide intertwine to form a ß-double helix structure, and it is stabilized by inter-strand hydrogen bonds. The peptides with chiral (E)-α,ß-unsaturated γ-amino acids derived from α-L-amino acids adopt a (P)-ß-double helix, whereas peptides consisting of (E)-α,ß-unsaturated γ-amino acids derived from α-D-amino acids adopt an (M)-ß-double helix conformation. The circular dichroism (CD) signature of the (P) and (M)-ß-double helices and the stability of these peptides at higher temperatures were examined. Furthermore, ion transport studies suggested that these peptides transport ions across membranes. Even though the structural analogy suggests that these new ß-double helices are structurally different from those of the α-peptide ß-double helices, they retain ion transport activity. The results reported here may open new avenues in the design of functional foldamers.

Vitamin D deficiency and genetic polymorphisms of vitamin D-associated genes in Parkinson's disease.

Parkinson's disease (PD) and vitamin D share a unique link as vitamin D deficiency (VDD) prevails in PD. Thus, an in-depth understanding of vitamin D biology in PD might be crucial for therapeutic strategies emphasising vitamin D. Specifically, explicating the effect of VDD and genetic polymorphisms of vitamin D-associated genes in PD, like VDR (vitamin D receptor) or GC (vitamin D binding protein) may aid the process along with polymorphisms of vitamin D metabolising genes (e.g., CYP2R1 and CYP27A1) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to vitamin D levels [GC (GC1-rs7041 and GC2-rs4588), CYP2R1, CYP24A1 and CYP27B1] and vitamin D function [VDR (FokI - rs2228570 and rs10735810; ApaI - rs7976091, rs7975232BsmI and rs1544410; and TaqI - rs731236)] was conducted to explore their relationship with PD severity globally. VDR-FokI polymorphism was reported to be significantly associated with PD in Hungarian, Chinese and Japanese populations, whereas VDR-ApaI polymorphism was found to affect PD in the Iranian population. However, VDR-TaqI and BsmI polymorphisms had no significant association with PD severity. Conversely, GC1 polymorphisms reportedly affected vitamin D levels without influencing the disease severity. CYP2R1 (excluding rs1993116) was also reportedly linked to clinical manifestations of PD. Genetic polymorphisms might cause VDD despite enough sunlight exposure and vitamin D-rich food intake, enhancing inflammation, there by influencing PD pathophysiology. Knowledge of the polymorphisms associated with VDD appears promising for developing precision vitamin D-dosing therapeutic strategies against PD.

Foldamer Nanotubes Mediated Label-Free Detection of Protein-Small Molecule Interactions.

Development of miniaturized lab-on-chip devices for the detection of rapid and specific small molecule-protein binding interactions at very low concentrations holds significant importance in drug discovery and biomedical applications. Here, the label-free detection of small molecule-protein interactions is reported on the surface functionalizable nanotubes of α,γ-hybrid peptide helical foldamers using nanoscale capacitance and impedance spectroscopy. The 12-helix conformation of the α,γ-hybrid peptide observed in the single crystals, self-assembled into nanotubes in an aqueous environment with exposed cysteine thiols for small molecule conjugation. The binding of streptavidin to the covalently linked biotin on the surface of nanotubes was detected at the picomolar concentrations. No change in the capacitance and impedance were observed in the absence of either immobilized biotin or protein streptavidin. The functionalizable hybrid peptide nanotubes reported here pave the way for the label-free detection of various small molecule protein interactions at very low concentrations.

Anion Tuned Structural Modulation and Nonlinear Optical Effects of Metal-Ion Directed 310 -Helix Networks.

Metals play an important role in the structure and functions of various proteins. The combination of metal ions and peptides have been emerging as an attractive field to create advanced structures and biomaterials. Here, we are reporting the anion-influenced, silver ion coordinated diverse networks of designed short tripeptide 310 -helices with terminal pyridyl groups. The short peptides adopted classical right-handed, left-handed and 310 EL -helical conformations in the presence of different silver salts. The peptides have displayed conformational flexibility to accommodate different sizes and interactions of anions to yield a variety of metal-coordinated networks. The complexes of metal ions and peptides have shown different porous networks, right- and left-handed helical polymers, transformation of helix into superhelix and 2 : 2 metal-peptide macrocycles. Further, the metal-peptide crystals with inherent dipoles of helical peptides gave striking second harmonic generation response. The optical energy upconversion from NIR to red and green light is demonstrated. Overall, we have shown the utilization of short 310 -helices for the construction of diverse metal-coordinated helical networks and notable non-linear optical effects.

Stereoselective synthesis of backbone extended π-conjugated amino esters.

Utilization of the Wittig reaction to synthesize conjugative multiple double bonds is rare. We examined the utility of the Wittig reaction to construct conjugative two and three carbon-carbon double bonds on the N-protected amino acid backbone. The ethyl esters of N-Boc amino acids with multiple carbon-carbon double bonds in the backbone were isolated in excellent yields with exceptional E-selectivity of the double bonds. The allylic alcohols of α,ß-unsaturated γ-amino esters were selectively synthesized from the DIBAL-H and BF3·OEt2. The allylic alcohols were transformed into aldehydes using IBX oxidation. Using this protocol, we synthesized ethyl esters of N-Boc-(E,E)-α,ß,γ,δ-unsaturated ε-amino acids with various side-chain functionalities and ethyl esters of N-Boc-(E,E,E)-α,ß,γ,δ,ε,ζ-unsaturated η-amino acids with excellent yields. We speculated the exceptional E-selectivity is probably due to the stabilization of the planar transition state of the Wittig reaction with the double bond p-orbitals. No racemization was observed in the synthesis of amino acids. The reported process may serve as an excellent route to synthesize multiple conjugative carbon-carbon double bonds.

Self-care practices and quality of life of filariasis patients in a gram panchayat of Paschim Burdwan district, West Bengal, India.

Background & objectives: Self-care management is one of the important components in the goal of elimination of lymphatic filariasis (LF) and Quality of Life (QoL) has become an important deliverable in the present day health care system. The objective was to assess the self-care management of the affected limb and to find out the quality of life who were suffering from lymphoedema. Methods: This was a community-based cross-sectional epidemiological study conducted during 2019-2020 in a Gourbazar gram panchayat area of Paschim Burdwan district of West Bengal, India. QoL was assessed by Lymphatic Filariasis Specific Quality of life Questionnaire (LFSQQ). Results: Total 115 LF patients were identified with a mean age of 53.9 years. About 26.1% correctly knew the management of the affected area. Out of the 33 patients having cracked skin, around 39.4% used to take care of the affected skin. Overall, median quality of life score was found to be 77.84 (65.90-89.20). Age-wise, median score gradually decreased with increase in age except in the age group of 50-60 years. Males had higher score compared to females (79.54 vs. 76.13). Activity domain score was found to be lowest followed by mobility score, while social and psychological domain score was found to be good. Interpretation & conclusion: Self-care practice is not known to the affected patients. Time has also come to integrate measures like rehabilitation, psychological intervention, social assistance in addition to self-care management to put up a holistic approach of the existing program.

Sequence dependent folding motifs of the secondary structures of Gly-Pro and Pro-Gly containing oligopeptides.

Folding motifs of the secondary structures of peptides and proteins are primarily based on the hydrogen bonding interactions in the backbone as well as the sequence of the amino acid residues present. For instance, the ß-turn structure directed by the Pro-Gly sequence is the key to the ß-hairpin structure of peptides/proteins as well as a selective site for the enzymatic hydroxylation of pro-collagen. Herein, we have investigated the sequence dependent folding motifs of end-protected Gly-Pro and Pro-Gly dipeptides using a combination of gas phase laser spectroscopy, quantum chemistry calculations, solution phase IR and NMR spectroscopy and single crystal X-Ray diffraction (XRD). All three observed conformers of the Gly-Pro peptide in the gas phase have been found to have extended ß-strand or polyproline-II (PP-II) structures with C5-C7 hydrogen bonding interactions, which correlates well with the structure obtained from solution phase spectroscopy and XRD. On the other hand, we have found that the Pro-Gly peptide has a C10/ß-turn structure in the solution phase in contrast to the C7-C7 (i.e. 27-ribbon) structure observed in the gas phase. Although the lowest energy structure in the gas phase is not C10, we find that C7-C7 is an abundantly found structural motif of Pro-Gly containing peptides in the Cambridge Structural Database, indicating that the gas phase conformers are not sampling any unusual forms. We surmise that the role of the solvent could be crucial in dictating the preferential stabilization of the C10 structure in the solution phase. The present investigation provides a comprehensive picture of the folding motifs of the Gly-Pro and Pro-Gly peptides observed in the gas phase and condensed phase weaving a fine interplay of the intrinsic conformational properties, solvation, and crystal packing of the peptides.

Metal-Coordinated Supramolecular Polymers from the Minimalistic Hybrid Peptide Foldamers.

Availing the peptide folded architectures to design metal-coordinated frameworks and cages is restricted due to the scarcity of readily accessible short and stable secondary structures. The secondary structures, α-helix and ß-sheets, play significant roles in stabilizing tertiary folds of proteins. Designing such helical structures from the short sequences of peptides without having any steric restrictions is exceptionally challenging. Here we reveal the short α,γ-hybrid tripeptide sequences that manifest stable helical structures without having any sterically constrained amino acids. These short hybrid tripeptides fold into helices even in the presence of two typically ß-sheet favoring Val residues. The hybrid helix consisting of terminal pyridine units coordinates with the metal ions and drives the helical polymerization. Depending on the sequence and the position of N in pyridine moieties, these peptides form selective metallogels with Ag+ and Cu2+ ions. The X-ray diffracted analysis of the peptide single crystals obtained from the gel matrix reveals that the helical structure is maintained during the self-assembly process. Further, by varying the counter anion, a 3D helical crystalline coordination polymer with permanent porosity is generated. The findings reported here can be used to design new functional metal-foldamer coordinated polymers.

Multi-C-C/C-N-Coupled Light-Emitting Aliphatic Terpolymers: N-H-Functionalized Fluorophore Monomers and High-Performance Applications.

To circumvent costly fluorescent labeling, five nonconventional, multifunctional, intrinsically fluorescent aliphatic terpolymers (1-5) have been synthesized by C-C/C-N-coupled, solution polymerization of two non-emissive monomers with protrusions of fluorophore monomers generated in situ. These scalable terpolymers were suitable for sensing and high-performance exclusion of CuII , logic function, and bioimaging. The structures of the terpolymers, in situ attachment of fluorescent monomers, aggregation-induced enhanced emission, bioimaging ability, and super adsorption were investigated by 1 H and 13 C NMR, EPR, FTIR, X-ray photoelectron, UV/Vis, and atomic absorption spectroscopy, thermogravimetric analysis, high-resolution transmission electron microscopy, dynamic light scattering, solid-state fluorescence, fluorescence imaging, and fluorescence lifetime measurements, as well as by isotherm, kinetics, and thermodynamic studies. The geometries and electronic structures of the fluorophores and the absorption and emission properties of the terpolymers were examined by DFT, time-dependent DFT, and natural transition orbital analyses. For 1, 2, and 5, the limits of detection were determined to be 1.03×10-7 , 1.65×10-7 , and 1.77×10-7 m, respectively, and the maximum adsorption capacities are 1575.21, 1433.70, and 1472.21 mg g-1 , respectively.

Synthesis of Biocompatible Aliphatic Terpolymers via In Situ Fluorescent Monomers for Three-in-One Applications: Polymerization of Hydrophobic Monomers in Water.

Biocompatible, nonconventional, multifunctional, purely aliphatic, light-emitting terpolymers, i.e., acrylonitrile-co-3-(N-isopropylacrylamido)propanenitrile-co-N-isopropylacrylamide (AN-co-NIPAMPN-co-NIPA, 1) and acrylonitrile-co-3-(N-hydroxymethylacrylamido)propanenitrile-co-N-hydroxymethylacrylamide (AN-co-NHMAMPN-co-NHMA, 2), were designed and synthesized via N-H-functionalized C-C + N-C-coupled in situ protrusions/grafting of fluorophore monomers, i.e., NIPAMPN and NHMAMPN, by solution polymerization of two highly hydrophobic nonemissive monomers in water. These scalable and reusable 1 and 2 were suitable for high-performance three-in-one applications, such as Fe(III) sensors, imaging of Madin-Darby canine kidney (MDCK) and human lung cancer (A549) cells, and security inks. The structures of 1 and 2, N-C-coupled in situ attachments/grafting of third fluorophore monomers, grafting events, and aggregation-enhanced emissions (AEEs), were analyzed by 1H and 13C NMR spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, thermogravimetric (TG) analysis, high-resolution transmission electron microscopy (HRTEM), dynamic light scattering (DLS), fluorescence imaging, and fluorescence lifetime. The geometries, electronic structures, and absorption/emission properties of 1 and 2 at optimized compositions were examined by density functional theory (DFT), time-dependent DFT (TDDFT), and natural transition orbital (NTO) analyses. The limits of detection were 3.20 × 10-7 and 1.37 × 10-7 M for 1 and 2, respectively. The excellent biocompatibility of 1 and 2 was confirmed by >95% retention of MDCK and A549 cell morphologies.

Observation of a weak intra-residue C5 hydrogen-bond in a dipeptide containing Gly-Pro sequence.

Specific folded structures of peptides and proteins depend on the sequence of various amino acid residues as well as different types of noncovalent interactions induced by the backbone as well as side-chains of those residues. In general, secondary structures of peptides and proteins are stabilized by C6 (δ-turn), C7 (γ-turn), C10 (ß-turn), C13 (α-turn), and C15 (π-turn) hydrogen-bonded rings formed through inter-residue interactions. However, it has been reported recently that an intraresidue C5 hydrogen-bond, which is relatively weak in strength, can contribute significantly to the stability of peptides and proteins. The C5 hydrogen-bond is mostly present in the ß-sheet structures of peptides and proteins along with other inter-residue noncovalent interactions. In this work, we have studied structures and conformational preferences of a dipeptide Z-Gly-Pro-OH (Z = benzyloxycarbonyl) using mass-selected vibrationally resolved electronic spectroscopy and IR-UV double resonance spectroscopy coupled with quantum chemistry calculations. Two conformers of the peptide are observed in the experiment. One of the conformers has an extended ß-strand type structure stabilized by C5 hydrogen-bonding, while the other one is folded through O-H ⋯ π interaction. The noncovalent interactions present in the two observed structures of the peptide are validated by natural bond orbital and noncovalent interaction calculations.

Metal-Helix Frameworks from Short Hybrid Peptide Foldamers.

The potential of structured peptides has not been explored much in the design of metal-organic frameworks (MOFs). This is partly due to the difficulties in obtaining stable secondary structures from the short α-peptide sequences. Here we report the design, crystal conformations, coordination site dependent different silver coordinated frameworks of short α,γ-hybrid peptide 12-helices consisting of terminal pyridyl moieties and the utility of metal-helix frameworks in the adsorption of CO2 . Upon silver ion coordination the 12-helix terminated by the 3-pyridyl derivatives adopted a 2:2 macrocyclic structure, while the 12-helix terminated by the 4-pyridyl derivatives displayed remarkable porous metal-helix frameworks. Both head-to-tail intermolecular H-bonds of the 12-helix and metal ion coordination have played an important role in stabilizing the ordered metal-helix frameworks. The studies described here open the door to design a new class of metal-organic-frameworks from peptide foldamers.

Artificial ß-Double Helices from Achiral γ-Peptides.

Double helices are not common in polypeptides and proteins except in the peptide antibiotic gramicidin A and analogous l,d-peptides. In contrast to natural polypeptides, remarkable ß-double-helical structures from achiral γ-peptides built from α,ß-unsaturated γ-amino acids have been observed. The crystal structures suggest that they adopted parallel ß-double helical structures and these structures are stabilized by the interstrand backbone amide H-bonds. Furthermore, both NMR spectroscopy and fluorescence studies support the existence of double-helical conformations in solution. Although a variety of folded architectures featuring distinct H-bonds have been discovered from the ß- and γ-peptide foldamers, this is the first report to show that achiral γ-peptides can spontaneously intertwine into ß-double helical structures.

Moringa oleifera Lam. seed extract prevents fat diet induced oxidative stress in mice and protects liver cell-nuclei from hydroxyl radical mediated damage.

High fat diet (HFD) prompts metabolic pattern inducing reactive oxygen species (ROS) production in mitochondria thereby triggering multitude of chronic disorders in human. Antioxidants from plant sources may be an imperative remedy against this disorder. However, it requires scientific validation. In this study, we explored if (i) Moringa oleifera seed extract (MoSE) can neutralize ROS generated in HFD fed mice; (ii) protect cell-nuclei damage developed by Fenton reaction in vitro. Swiss mice were fed with HFD to develop oxidative stress model (HFD group). Other groups were control, seed extract alone treated, and MoSE simultaneously (HS) treated. Treatment period was of 15 days. Antioxidant enzymes with tissue nitrite content (TNC) and lipid peroxidation (LPO) were estimated from liver homogenate. HS group showed significantly higher (P < 0.05) superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) activity, and ferric reducing antioxidant power (FRAP) compared to only HFD fed group. Further, TNC and LPO decreased significantly (P < 0.05) in HS group compared to HFD fed group. MoSE also protected hepatocytes nuclei from the hydroxyl radicals generated by Fenton reaction. MoSE was found to be polyphenol rich with potent reducing power, free radicals and hydroxyl radicals scavenging activity. Thus, MoSE exhibited robust antioxidant prospective to neutralize ROS developed in HFD fed mice and also protected the nuclei damage from hydroxyl radicals. Hence, it can be used as herbal medication against HFD induced ROS mediated disorders.

Quercetin and beta-sitosterol prevent high fat diet induced dyslipidemia and hepatotoxicity in Swiss albino mice.

High fat diet group showed a significant rise in serum and hepatic total cholesterol, triglyceride and atherogenic index which are major biomarkers of dyslipidemia and cardiovascular risk. The liver function markers, lipid peroxidation and proinflammatory cytokine levels were elevated in high fat diet group whereas antioxidant levels significantly reduced. These findings manifest hepatic damage which was further confirmed by histological findings. Quercetin and beta-sitosterol though structurally different yet both ameliorate the sickening changes in different mechanism. The current investigation is perhaps the first report of the mechanistic role of two polyphenols over dyslipidemia and subsequent hepatotoxicity.

Seabuckthron (Hippophae rhamnoides L.) leaf extract ameliorates the gamma radiation mediated DNA damage and hepatic alterations.

In vitro assessment showed that H. rhamnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (gamma) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of beta radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkappaB (p65) and IkappaBalpha increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures.

Role of Influenza A virus protein NS1 in regulating host nuclear body ND10 complex formation and its involvement in establishment of viral pathogenesis.

Influenza viral infection is a seasonal infection which causes widespread acute respiratory issues among humans globally. This virus changes its surface receptor composition to escape the recognition process by the host's immune cells. Therefore, the present study focussed to identify some other important viral proteins which have a significant role in establishment of infection and having apparent conserved structural composition. This could facilitate the permanent vaccine development process or help in designing a drug against IAV (influenza A virus) infection which will eliminate the seasonal flu shot vaccination process. The NS1 (Non-structural protein 1) protein of IAV maintains a conserved structural motif. Earlier studies have shown its significant role in infection establishment. However, the mechanism by which viruses escape the host's ND10 antiviral action remains elusive. The present study clearly showed that IAV infection and NS1 transfection in A549 cells degraded the main component of the ND10 anti-viral complex, PML and therefore, inhibited the formation of Daxx-sp100-p53-PML complex (ND10) at the mid phase of infection/transfection. PML degradation activated the stress axis which increased cellular ROS (reactive oxygen species) levels as well as mitochondrial dysfunction. Additionally, IAV/NS1 increased cellular stress and p53 accumulation at the late phase of infection. These collectively activated apoptotic pathway in the host cells. Along with the inactivation of several interferon proteins, IAV was found to decrease p-IKKε. A549 cells transfected with pcDNA3.1-NS1 showed a similar effect in the interferon axis and IKKε. Moreover, NS1 induced the disintegration of the host's ND10 complex through the changes in the SUMOylation pattern of the PML nuclear body. These findings suggest the possible mechanism of how NS1 helps IAV to establish infection in the host cells. However, it demands further detailed study before targeting NS1 to develop permanent vaccines or novel drugs against IAV in future.

Association of dopamine receptor D3 polymorphism with Levodopa-induced Dyskinesia: A study on Parkinson's disease patients from India.

INTRODUCTION: Levodopa-induced dyskinesia (LID) is a debilitating motor feature in a subset of patients with Parkinson's disease (PD) after prolonged therapeutic administration of levodopa. Preliminary animal and human studies are suggestive of a key role of dopamine type 3 (D3) receptor polymorphism (Ser9Gly; rs6280) in LID. Its contribution to development of LID among Indian PD patients has remained relatively unexplored and merits further investigation. METHODS AND MATERIALS: 200 well-characterised PD patients (100 without LID and 100 with LID) and 100 age-matched healthy controls were recruited from the outpatient department of Institute of Neurosciences Kolkata. MDS-UPDRS (Unified Parkinson's Disease Rating Scale from International Movement Disorder Society) Part III and AIMS (abnormal involuntary movement scale) were performed for estimation of severity of motor features and LID respectively in the ON state of the disease. Participants were analysed for the presence of Ser9Gly single nucleotide variant (SNV) (rs6280) by polymerase chain reaction followed by restriction fragment length polymorphism techniques. RESULTS: The frequency of AA genotype (serine type) was more frequently present in PD patients with LID compared to PD patients without LID (50 % vs 28 %; P = 0.002; OR = 2.57, 95 % CI: 1.43 - 4.62). The abnormal involuntary movement scale score was significantly higher in PD patients with AA genotype compared to carriers of glycine allele (AG + GG) (4.08 ± 3.35; P = 0.002). CONCLUSION: We observed a significant association of serine type SNV (rs6280) in D3 receptor gene in a cohort of PD patients with LID from India. More severe motor severity was found in patients with glycine substitution of the same SNV. The current study emphasised the role of D3 receptor in the pathogenesis of LID.