Loading

JSM Alzheimer's Disease and Related Dementia

Neurophysiological Changes in Oxidative Injury: Involvement of Calcium Homeostasis and ER Stress

Short Communication | Open Access Volume 4 | Issue 1 |

  • 1. Drug Development Diagnostics & Biotechnology Division, Indian Institute of Chemical Biology, India
+ Show More - Show Less
Corresponding Authors
Sibani Sarkar, Drug Development Diagnostics & Biotechnology Division, Indian Institute of Chemical Biology, CSIR, 4, Raja SC. Mullick Road, Kolkatta-32, India
Abstract

Endoplasmic reticulum (ER), a multifunctional organelle, plays an important role in the maintenance of intracellular calcium homeostasis and regulation of cell death. Cellular stress conditions such as glucose deprivation, depletion of ER calcium stores and exposure to free radicals that interfere with ER function lead to the accumulation and aggregation of proteins. ER stress can be developed by disrupting its homeostasis in neurological diseases and by disturbances in calcium or redox status. Thus, increase in the cytosolic calcium is one of the important aspects in brain diseases which may contribute to oxidative stress injury and cell death. ER stress plays a vital role in neuronal cell death.

Azheimer disease (AD) is a common neurodegenerative disease which is a frustrating clinical problem and is one of the leading cause of death worldwide. In neurodegenerative diseases and in aging, free - radical generation is the common cause of tissue injury and cell death. Imbalance between ROS productions and antioxidant levels result in development of oxidative stress which through a series of events deregulates the cellular functions and leads to premature aging. Excessive increase of Ca+2 in mitochondrial matrix, the permeability of mitochondria changed and finally resulted in MPT pore opening followed by release of cytochrome C and other proapoptotic factors into the cytoplasm. The released cytochrome C then activates caspase 3 to initiate cell death. ER Stress leads to the activation of unfolded protein response (UPR) and governs the recovery of homeostasis. Otherwise, UPR fails to restore normal function in chronic ER stress and results in apoptosis of irreversibly damaged cells.

In this communication, the role of unfolded protein response (UPR) in neurodegeneration induced ER stress and its modulation will be described. It also will be illustrated the mechanism of age-associated declines in cellular function and progressive failure of chaperoning system. Thus, the protective role of free and nanoformulated compounds in reducing stress generation during AD especially in aging will also be elucidated.

Keywords
  •  Azheimer disease
  •  Unfolded protein response
CITATION

: Sarkar S, Mandal A (2017) Neurophysiological Changes in Oxidative Injury: Involvement of Calcium Homeostasis and ER Stress. JSM Alzheimer’s Dis Related Dementia 4(1): 1033

INTRODUCTION

Endoplasmic reticulum (ER) stress induced cell death plays an important role in neurodegenerative diseases. Alzheimer is a patho physiological ER stressor [1-3]. Several studies have shown that AD causes a severe impairment of ER function, which in turn triggers shut down of protein translation and apoptosis [4,5] suggesting that ER plays an important role in Alzheimer diseases. Endoplasmic reticulum (ER) stress plays a vital role in mediating neuronal cell death. Under various pathological situations, these physiological functions of the ER are perturbed resulting in so called ER stress and can lead to the accumulation of the newly synthesized unfolded proteins in the ER. The molecular mechanisms of ER damage in neurodegenerative diseased neurons are not clear [6]. But a number of in vitro studies have demonstrated that ER function is sensitive to oxidative stress [7-9]. The Endoplasmic reticulum (ER) is branched tubule and flattened sac network which is an extension of nuclear envelop and connect to the golgi complex. The ER is also one of the organelle that produces reactive oxygen species (ROS) robustly in the neurodegenerative disorder in the brain [10,11] as a result of oxidative stress. So, ROS are involved in neuronal cell death as they damage the ER. ER has various functions such as protein folding, post translational modification and maintenance of cellular calcium homeostasis [11,12].

Among the stimuli that promote ER stress are ischemia, inflammation and disorders that impair the ER’s ability to properly fold peptides or eliminate unfolded proteins [13]. Neurodegenerative disordered diseases such as AD induces ER stress, which is characterized by the accumulation of proteins in the ER [13], leading to the activation of several pathways to restore normal ER function [14]. If, however, ER function is severely impaired and cellular homeostasis cannot be restored, apoptosis of the neuron is induced. ER stress triggers the activation and expression of a number of proteins, including upregulation of the transcription factor CHOP (C/EBP-homologous protein also known as C/EBP), growth arrest- and DNA damage inducible gene 153 [GADD153] or DNA-damage inducible transcript 3 [DDIT3]). CHOP belongs to the C/EBP transcription factor family and has been shown to trigger apoptosis [15].

Changes in the Ca+2 level in the ER elicit ER stress, a universal cellular response, which through three ER sensors (PERK, IRE1α, and ATF6) blocks translation and up regulates genes that first mount an anti apoptotic response. Only if the disturbance cannot be overcome and the signal persists, apoptosis is induced [16]. A-beta production inhibition or immunization strategies in the first line failed to cure AD. This suggests that ER stress is one of the cellular pathologies induced by AD. Due to increased oxidative stress, accumulation of unfolded proteins and metabolic disturbances are observed in AD [17]. ER is one cellular organelle that is related to stress mediation by its multifunctionality that ER assists and closely related to monitor quality of ascent proteins [18]. To eliminate the toxic protein components cells activate an adaptive mechanism that consist of a number of intracellular signaling pathway collectively known as the unfolded protein response (UPR) [19,20]. However during prolonged or overwhelming ER stress, UPR fails to restore the normal function of the ER and apoptotic cascade will be activated [21-23] .

ER stress can also be initiated by the accumulation of unfolded proteins in the organelle which causes the release of Ca+2. The mitochondrion as well as ER plays an important role in the regulation of cellular calcium homeostasis [24]. Under prolonged ER stress condition as happens in the different neurodegenerative disordered diseases, a slow but sustained increase in the mitochondrial matrix free Ca+2 occur, which can reach a critical threshold to trigger the opening of mitochondrial permeability transition pore (MPTP) and initiate the apoptotic cascade [25]. The ER can play an important role in regulating apoptosis by adjusting the load of Ca+2 upon the mitochondrion. So, the reduction in Ca+2 in the mitochondria which can be released from ER decrease the probability of apoptosis [26-28]. The over expression of the anti apoptotic protein BCL2 can influence the distribution of Ca+2 within the ER/mitochondrial complex. Other anti apoptotic protein, AKT also results in reduced ER Ca+2 release, and diminished cellular sensitivity to Ca+2 mediated apoptotic stimuli [26,29] Anti apoptotic proteins BCL2 and AKT affect calcium homeostasis

By down regulating translation and up regulating transcription of ER resident enzymes and chaperons, UPR acts primarily to protect against ER stress. However the sustained activation of UPR effectors can lead to an apoptotic phenotype via CHOP transcription and translation and by caspase12 activation. It is this “double edged sword” feature of the UPR that has made it as an attractive model as a contributor to cell death. If indeed AD causes ER stress and activates the UPR, the resultant molecular cascades could contribute to either cell survival or death.

Alzheimer disease, a progressive neurodegenerative disorder, leads to dementia by involving a gradual declination of many cognitive processes. Amyloid β peptides and neurofibrillary tangles are accumulated at the onset of AD. ER can recognize disturbances in cellular homeostasis. So, ER stress is an indicator of AD [30] and it plays an important role to reduce AD in the brain. Thus reducing ER stress may provide a process to reduce β peptide accumulation. In this context, it is worth mentioning that many native plant products were found to demonstrate the effectiveness to fight numerous diseases including AD. Based on range, flexibility, ease of access, relatively low cost, low levels of technological input, relative low side effects of traditional medicine (WHO 2002), there is a critical need to mainstream traditional medicine into public health care to achieve the objectives of improved access to healthcare facilities.

So, it is therefore proposed to look into effective therapeutic agents from Indian plants to promote human health by inhibiting different neurodegenerative diseases specially AD. This communication tells us to reduce AD by inhibiting ER stress by using native plant products. Due to limitations posed by the restrictive BBB, it is very difficult to administer required drugs at right concentrations in the diseased cells. Thus, new therapeutics and novel delivery approaches with the capacity to successfully cross the BBB is critically needed. Nanotechnologies hold great promise in AD treatment as the nanoencapsulated drugs can easily cross the BBB, protect therapeutic agents and even allow its sustained release. It has been observed from previous studies [31] that nanovesiculated drug delivery mode was the most effective to combat neurodegenerative disorders in comparison to other vesicular mode. These findings would possibly lead to provide new insights into the molecular pathways of disease and pharmacological manipulation for blocking the disease.

REFERENCES

 

  1. Paschen W, Doutheil J. Disturbances of the functioning of endoplasmic reticulum: a key mechanism underlying neuronal cell injury? J Cereb Blood Flow Metab. 1999; 19: 1-18.
  2. Paschen W, Frandsen A. Endoplasmic reticulum dysfunction--a common denominator for cell injury in acute and degenerative diseases of the brain? J Neurochem. 2001; 79: 719-725.
  3. Hoozemans JJ, Veerhuis R, Van Haastert ES, Rozemuller JM, Baas F, Eikelenboom P, et al. The unfolded protein response is activated in Alzheimer's disease. Acta Neuropathol. 2005; 110: 165-172.
  4. Matus S, Glimcher LH, Hetz C. Protein folding stress in neurodegenerative diseases: a glimpse into the ER. Curr Opin Cell Biol. 2011; 23: 239-252.
  5. Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999; 397: 271-274.
  6. Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium. 2002; 32: 235-249.
  7. Dreher D, Jornot L, Junod AF. Effects of hypoxanthine-xanthine oxidase on Ca2+ stores and protein synthesis in human endothelial cells. Circ Res. 1995; 76: 388-95.
  8. Racay P, Kaplán P, Lehotský J, Mézesová V. Rabbit brain endoplasmic reticulum membranes as target for free radicals. Changes in Ca(2+)-transport and protection by stobadine. Biochem Mol Biol Int. 1995; 36: 569-577.
  9. Viner RI, Huhmer AFR, Bigelow DJ, Schoneich C. The oxidative inactivation of sarcoplasmic reticulum Ca2+-ATPase by peroxynitrite. Free Radic Res. 1996; 24: 243-259.
  10. Halliwell B, Gutteridge JMC. Oxidative stress: Adaptation, damage, repair and death. In: Free radicals in biology and medicine. Halliwell B, Gutteridge JMC, editors. New York, NY: Oxford University Press. 1999.
  11. Lewén A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma. 2000; 17: 871-890.
  12. Baumann O, Walz B. Endoplasmic reticulum of animal cells and its organization into structural and functional domains. Int Rev Cytol. 2001; 205: 149-214.
  13. Dobson CM. Protein folding and misfolding. Nature. 2003; 426: 884-890.
  14. Gorlach A, Klappa P, Kietzmann T. The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. Antioxid Redox Signal. 2006, 8: 1391-1418.
  15. Maytin EV, Ubeda M, Lin JC, Habener JF. Stress-inducible transcription factor CHOP/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms. Exp Cell Res. 2001; 267: 93-104.
  16. Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 2006; 7: 880-885.
  17. LaFerla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci. 2007; 8: 499-509.
  18. Benham AM. Protein secretion and the endoplasmic reticulum. Cold Spring Harb Perspect Biol. 2012; 4: a012872.
  19. Schröder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem. 2005; 74: 739-789.
  20. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007; 8: 519-529.
  21. Kim I, Xu W, Reed JC. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 2008; 7: 1013-1030.
  22. Xu C, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest. 2005; 115: 2656-2664.
  23. Basseri S, Austin RC. Endoplasmic reticulum stress and lipid metabolism: mechanisms and therapeutic potential. Biochem Res Int. 2012; 2012: 841362.
  24. Ruiz A, Matute C, Alberdi E. Endoplasmic reticulum Ca2+ release through ryanodine and IP3 receptors contributes to neuronal excitotoxicity. Cell Calcium. 2009; 46: 273-281.
  25. Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 2004; 11: 372-380.
  26. Marchia S, Rimessia A, Giorgia C, Baldinia C, Ferronia L, Rizzutoa R, et al. Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+- dependent apoptotic stimuli. Biochem Biophys Res Communications. 2008; 375:  501-505.
  27. Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 2003; 300: 135-139.
  28. Szado T, Vanderheyden V, Parys JB, De Smedt H, Rietdorf K, Kotelevets L, et al. Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis. Proc Natl Acad Sci U S A. 2008; 105: 2427-2432.
  29. Hoozemans JJ, van Haastert ES, Nijholt DA, Rozemuller AJ, Eikelenboom P, Scheper W. The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. Am J Pathol. 2009; 174: 1241-51.
  30. Das S, Mandal AK, Ghosh A, Panda S, Das N, Sarkar S. Nanoparticulated Quercetin in combating age related cerebral oxidative injury. Curr Aging Sci. 2008; 1: 169-174.
  31. Ghosh A, Sarkar S, Mandal AK, Das N. Neuroprotective role of nanoencapsulated quercetin in combating ischemia-reperfusion induced neuronal damage in young and aged rats. PLoS One. 2013; 8: e57735.

Sarkar S, Mandal A (2017) Neurophysiological Changes in Oxidative Injury: Involvement of Calcium Homeostasis and ER Stress. JSM Alzheimer’s Dis Related Dementia 4(1): 1033

Received : 10 Dec 2016
Accepted : 31 Aug 2017
Published : 02 Sep 2017
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X