Exploring the role of Nrf2 signaling in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the most aggressive glial cell tumors in adults. Although current treatment options for GBM offer some therapeutic benefit, median survival remains poor and does not generally exceed 14 months. Several genes, such as isocitrate dehydrogenase (IDH) enzyme and O6-methylguanine-DNA methyltransferase (MGMT), have been implicated in pathogenesis of the disease. Treatment is often adapted based on the presence of IDH mutations and MGMT promoter methylation status. Recent GBM cell line studies have associated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) expression with high-grade tumors. Increased Nrf2 expression is often found in tumors with IDH-1 mutations. Nrf2 is an important transcription factor with anti-apoptotic, antioxidative, anti-inflammatory, and proliferative properties due to its complex interactions with multiple regulatory pathways. In addition, evidence suggests that Nrf2 promotes  GBM cell survival in hypoxic environment,by up-regulating hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Downregulation of Nrf2 has been shown to improve GBM sensitivity to chemotherapy drugs such as Temozolomide. Thus, Nrf2 could be a key regulator of GBM pathways and potential therapeutic target.  Further research efforts exploring an interplay between Nrf2 and major molecular signaling mechanisms could offer novel GBM drug candidates with a potential to significantly improve patients prognosis.

Repurposing food molecules as a potential BACE1 inhibitor for Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of ß-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave ß-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of ß-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R 2 = 0.82, Q 2 loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = -8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate's inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.

Comparative Potential of Zinc Sulfate, L-Carnitine, Lycopene, and Coenzyme Q10 on Cadmium-Induced Male Infertility.

The human exposure to toxic chemicals and heavy metals is one of the main predisposing factors contributing to male infertility. Acute exposure to cadmium chloride results in testicular damage and infertility. The purpose of the present study was to investigate and compare the curative effect of coenzyme Q10 (CoQ10), lycopene, L-carnitine (LC), and zinc sulfate against the cadmium-induced infertility in male Wistar rats. Cadmium chloride (0.4 mg/kg/day) was orally administered to rats for three consecutive days. Then, oral administration of different treatments (i.e., LC 100 mg/kg, CoQ10 20 mg/kg, lycopene 4 mg/kg, zinc sulfate 6 mg/kg, and a combination LC-CoQ10 at 500/50 mg/kg) was carried out for 30 days. The impact of different treatments on semen parameters, such as sperm count and motility, testicular antioxidants, and serum testosterone, was determined. Furthermore, the morphology of epididymis sperms and histopathology of rat testes were also assessed. Cadmium exposure decreased the sperm count, progressive sperm motility, testosterone, superoxide dismutase (SOD), and catalase and reduced glutathione (GSH). It also caused banana sperm tail, bent sperm head, vacuolization of seminiferous tubules, and oligospermia in rat testes. All treatments with nutraceuticals improved sperm count, sperm morphology, serum testosterone, vacuolization of seminiferous tubules, and oligospermia in diseased rats. Treatment with lycopene, LC, and LC-CoQ10 improved progressive sperm motility and other parameters and increased SOD, GSH, and CAT in the rat testes. CoQ10 also increased SOD activity in rat testes' tissue homogenates. It is concluded from the current study that all nutraceuticals partially improved reproductive toxicity of cadmium. The administration of lycopene and a high-dose combination of LC-CoQ10 were more efficacious in treating cadmium-induced infertility than other treatments. Treatment of cadmium-exposed rats with lycopene, LC, CoQ10, and LC-CoQ10 improved sperm count and motility through reduction of testicular oxidative stress and improving serum testosterone.

Exploring the management approaches of cytokines including viral infection and neuroinflammation for neurological disorders.

Considerable evidence supports that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in various neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. The purpose of this study is to discuss the recent research on treating cytokine storm and amyloids, including stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's condition, Multi-sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). Neuroinflammation observed in neurological disorders has a pivotal role in exacerbating Aß burden and tau hyperphosphorylation, suggesting that stimulating cytokines in response to an undesirable external response could be a checkpoint for treating neurological disorders. Furthermore, the pro-inflammatory cytokines help our immune system through a neuroprotective mechanism in clearing viral infection by recruiting mononuclear cells. This study reveals that cytokine applications may play a vital role in providing novel regulation and methods for the therapeutic approach to neurological disorders and the causes of the deregulation, which is responsible for neuroinflammation and viral infection. However, it needs to be further investigated to clarify better the mechanisms of cytokine release in response to various stimuli, which could be the central point for treating neurological disorders.

Emerging therapeutic developments in neurodegenerative diseases: A clinical investigation.

Despite a century of intensive research, there is still a lack of disease-modifying treatments for neurodegenerative diseases that pose a threat to human society. A well-documented knowledge and resource gap has impeded the translation of fundamental research into promising therapies. In addition, the analysis of extensive preclinical data to allow the improved selection of therapeutic technologies and clinical candidates for further development is challenging. To address this need, we describe technologies that have emerged over the past decade that have enabled the development of novel, high-quality, cost-effective treatments for major neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Moreover, we benchmark emerging technologies that have been adopted by top pharmaceutical companies looking to bridge the gap between drug discovery and drug development in neurodegenerative disease.

Link of BIN1, CLU, and IDE Gene Polymorphisms with the Susceptibility of Alzheimer's Disease: Evidence from a Meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common form of neurodegenerative disorder. The association of BIN1, CLU, and IDE genetic polymorphisms with AD risk have been evaluated overtimes that produced conflicting outcomes. OBJECTIVE: We performed this meta-analysis to investigate the contribution of BIN1 (rs744373 and rs7561528), CLU (rs11136000 and rs9331888), and IDE (rs1887922) polymorphisms to AD risk. METHODS: From a systemic literature search up to July 15, 2021, we included 25 studies with rs744373, 16 studies with rs7561528, 37 studies with rs11136000, 16 studies with rs9331888, and 4 studies with rs1887922. To analyze the correlation, we constructed seven genetic models that used odds ratio and 95% confidence intervals. We used RevMan 5.4 for meta-analysis. RESULTS: Our study suggests that BIN1 rs744373 is associated with a significantly increased risk of AD in five genetic models (OR>1). Again, CLU rs11136000 showed reduced association in all genetic models (OR<1). CLU rs9331888 revealed an increased association in two models (OR>1). The IDE rs1887922 showed significantly increased risk in four models (OR>1). From subgroup analysis, a significantly increased risk of AD was observed in Caucasians and Asians for BIN1 rs744373. Again, BIN1 rs7561528 showed a significantly enhanced risk of AD only in Caucasians. CLU rs11136000 showed significantly reduced risk in Caucasians but rs9331888 showed increased risk in the same ethnicity. CONCLUSION: Our meta-analysis confirms the association of BIN1 rs744373, CLU rs9331888, and IDE rs1887922 polymorphisms with an increased risk of AD, especially in Caucasians. Again, CLU rs11136000 is associated with reduced AD risk in the overall population and Caucasians.

Resveratrol and neuroprotection: an insight into prospective therapeutic approaches against Alzheimer's disease from bench to bedside.

Alzheimer's disease (AD) is the most common cause of dementia and cognitive impairment; yet, there is currently no treatment. A buildup of Aß, tau protein phosphorylation, oxidative stress, and inflammation in AD is pathogenic. The accumulation of amyloid-beta (Aß) peptides in these neurocognitive areas is a significant characteristic of the disease. Therefore, inhibiting Aß peptide aggregation has been proposed as the critical therapeutic approach for AD treatment. Resveratrol has been demonstrated in multiple studies to have a neuroprotective, anti-inflammatory, and antioxidant characteristic and the ability to minimize Aß peptides aggregation and toxicity in the hippocampus of Alzheimer's patients, stimulating neurogenesis and inhibiting hippocampal degeneration. Furthermore, resveratrol's antioxidant effect promotes neuronal development by activating the silent information regulator-1 (SIRT1), which can protect against the detrimental effects of oxidative stress. Resveratrol-induced SIRT1 activation is becoming more crucial in developing novel therapeutic options for AD and other diseases that have neurodegenerative characteristics. This review highlighted a better knowledge of resveratrol's mechanism of action and its promising therapeutic efficacy in treating AD. We also highlighted the therapeutic potential of resveratrol as an AD therapeutic agent, which is effective against neurodegenerative disorders.

Cognitive and affective disturbances in patients with Parkinson's disease: Perspectives for classifying of motor/neuropsychiatric subtypes.

Parkinson's disease (PD) is a neurological disorder, related to rigidity, bradykinesia, and resting tremors, among other motor symptoms. It is noticed in the increasing frequency of neuropsychiatric disorders, which may be also caused by non-motor symptoms of PD. Treatment of PD is usually based on the classification of motor subtypes; however, it remains unclear whether motor subtypes have differences in the severity of psychiatric symptoms. It determines the importance of discovering possible neuropsychiatric subtypes of PD. We conducted a clinical study, which included group 1 - patients with postural instability and gait disorders dominant (PIGD) subtype, group 2 - patients with tremor dominant (TD) and indeterminate subtypes (non-PIGD), and group 3 - people who did not have CNS damage. We used the Montreal Cognitive Assessment, Russified 20-point version of the Toronto Alexithymia Scale, State-Trait Anxiety Inventory, and Beck Depression Inventory for assessment of the mental status. It was the first time that neuropsychiatric subtypes of PD had been investigated based on the condition of cognition and mood. Cluster analysis gave us the possibility to classify our patients by the following subtype: affective-cognitive PIGD, anxious PIGD, affective-cognitive non-PIGD, and non-PIGD without psychiatric symptoms. This indicates a closed link between psychiatric and motor symptoms, which can be used for the improved treatment of PD.

Biomolecular alterations in acute traumatic brain injury (TBI) using Fourier transform infrared (FTIR) imaging spectroscopy.

Acute injury is one of the substantial stage post-traumatic brain injury (TBI) occurring at the moment of impact. Decreased metabolism, unregulated cerebral blood flow and direct tissue damage are triggered by acute injury. Understating the biochemical alterations associated with acute TBI is critical for brain plasticity and recovery. The objective of this study was to investigate the biochemical and molecular changes in hippocampus, corpus callosum and thalamus brain regions post-acute TBI in rats. Fourier Transform Infrared (FTIR) imaging spectroscopy were used to collect chemical images from control and 3 hrs post-TBI (Marmarou model was used for the TBI induction) rat brains and adjacent sections were treated by hematoxylin and eosin (H&E) staining to correlate with the disruption in tissue morphology and injured brain biochemistry. Our results revealed that the total lipid and total protein content decreased significantly in the hippocampus, corpus callosum and thalamus after brain injury. Reduction in lipid acyl chains (-CH2) associated with an increase in methyl (-CH3) and unsaturated lipids olefin = CH concentrations is observed. Furthermore, there is a decrease in the lipid order (disorder), which leads to an increase in acyl chain fluidity in injured rats. The results suggest acute TBI damages brain tissues mechanically rather than chemical alterations. This will help in assessing successful therapeutic strategy in order to mitigate tissue damage in acute TBI period.

Molecular Insight into the Therapeutic Promise of Targeting APOE4 for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes chronic cognitive dysfunction. Most of the AD cases are late onset, and the apolipoprotein E (APOE) isoform is a key genetic risk factor. The APOE gene has 3 key alleles in humans including APOE2, APOE3, and APOE4. Among them, APOE4 is the most potent genetic risk factor for late-onset AD (LOAD), while APOE2 has a defensive effect. Research data suggest that APOE4 leads to the pathogenesis of AD through various processes such as accelerated beta-amyloid aggregations that raised neurofibrillary tangle formation, cerebrovascular diseases, aggravated neuroinflammation, and synaptic loss. However, the precise mode of actions regarding in what way APOE4 leads to AD pathology remains unclear. Since APOE contributes to several pathological pathways of AD, targeting APOE4 might serve as a promising strategy for the development of novel drugs to combat AD. In this review, we focus on the recent studies about APOE4-targeted therapeutic strategies that have been advanced in animal models and are being prepared for use in humans for the management of AD.

NMDA Receptor Antagonists: Repositioning of Memantine as a Multitargeting Agent for Alzheimer's Therapy.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes problems with memory, thinking, and behavior. Currently, there is no drug that can reduce the pathological events of this degenerative disease but symptomatic relief is possible that can abate the disease condition. N-methyl-D-aspartate (NMDA) receptors exert a critical role for synaptic plasticity as well as transmission. Overstimulation of glutamate receptors, predominantly NMDA type, may cause excitotoxic effects on neurons and is recommended as a mechanism for neurodegeneration. Atypical activation of the NMDA receptor has been suggested for AD by synaptic dysfunction. NMDA receptor antagonists especially memantine block the NMDA receptor and can reduce the influx of calcium (Ca2+) ions into neuron, thus, toxic intracellular events are not activated. This review represents the role of NMDA receptors antagonists as potential therapeutic agents to reduce AD. Moreover, this review highlights the repositioning of memantine as a potential novel therapeutic multitargeting agent for AD.

Ionic gradient liposomes: Recent advances in the stable entrapment and prolonged released of local anesthetics and anticancer drugs.

Liposomes have established themselves as great pharmaceutical carriers over the past three decades. These phospholipid vesicular systems have undergone great technical advances including remote drug loading, targeted delivery, and combinatorial drug therapy. Ionic gradient liposomes (IGL) necessitates active loading of the drug in preformed vesicles exhibiting a transmembrane pH or ion gradient, with a low intra liposome pH (∼ 4-5), and a high outside pH (∼7-8). It allows high drug encapsulation and prolonged release, particularly for amphipathic weak acids and weak bases. Most local anesthetics (Bupivacaine, Ropivacaine, Tetracaine, and others) have a pka in the range of 7-9, which makes them ideal candidates for their entrapment in IGL. The same is true for most anthracyclines which have great anti-tumor properties (Doxorubicin, Daunorubicin, Idarubicin, and others). Many FDA approved liposomal drugs utilise ion gradient for their encapsulation. Considering their immense utility, we summarize here in this review, the recent contributions made by various research groups utilizing IGL, to accentuate the development of these carriers in drug delivery. This would possibly be helpful in carrying new investigations and further contributions in the optimization and advancements of new drugs for better therapeutics.

Proteins Commonly Linked to Autism Spectrum Disorder and Alzheimer's Disease.

Several years after the first publication of Barker's Hypothesis the identification of common patterns and pathways between genetic and epigenetic risk factors in neurodegenerative disorders is still an open problem. For the cases of Alzheimer's disease and Autism and by taking into consideration the increasing number of diagnosed cases globally, scientists focused on commonly expressed and related proteins like Amyloid beta and the mechanisms of their underlying dysfunctionalities. In this review paper, an attempt to specify significant correlations between proteins linked to Autism Spectrum Disorders and Alzheimer's Disease is presented. Both diseases are highlighted with an emphasis on the macromolecules that play a fundamental role in their development. These proteins are described and analyzed concerning the underlying pathology of these diseases.

Mitochondrial Dynamics and Proteins Related to Neurodegenerative Diseases.

Disruptions in the regulation of mitochondrial dynamics and the occurrence of proteins misfolding lead to neuronal death, resulting in Age-related Dementia and Neurodegenerative diseases as well as Frailty. Functional, neurophysiologic and biochemical alterations within the mitochondrial populations can reveal deficits in brain energy metabolism resulting in Mild Cognitive Impairment, abnormal neural development, autonomic dysfunction and other mitochondrial disorders. Additionally, in cases of Alzheimer's disease or Parkinson's disease, a significant number of proteins seem to form unordered and problematic structures, leading through unknown mechanisms to pathological conditions. While the proteins structure prediction problem is still an open challenge regarding its complexity, several features associated with the correlations of misfolding proteins and Neurodegeneration are discussed in the present study and a computational analysis for the proteins Amyloid Beta, Tau, α-Synuclein, Parkin, Pink1, MFN1, MFN1, OPA1, and DNM1L is also presented.

Impact of Hydroxyl Radical Modified-Human Serum Albumin Autoantigens in Systemic Lupus Erythematosus.

Free radicals are important mediators for cell toxicity and pathogenesis of diseases. Reactive oxygen species (ROS) have been generated broadly in inflammatory diseases including autoimmune diseases. ROS have been not only associated with the initiation and progression of the autoimmune response but also in amplification and exploring to novel epitopes, through the unveiling of antigenic determinants. This review explores the involvement of ROS in the pathophysiology of non-organ specific autoimmune diseases like systemic lupus erythematosus (SLE). The modification of human serum albumin through hydroxyl radical is thought to be responsible for the induction of autoantibodies against modified human serum albumin. In the light of overwhelming evidence suggesting the association with oxidative damage in autoimmunity, the administration of antioxidants could be a viable alternative for the neutralization of free radicals that are involved in eliciting autoimmune disease. In this review, we have discussed their pro-oxidant as well anti-oxidant properties which are capable of differentially modulating the autoimmune response.

Electrocatalytic Performance of Chemically Synthesized PIn-Au-SGO Composite toward Mediated Biofuel Cell Anode.

The proposed work intended to make an intellectual contribution to the domain of green nanotechnology which emphasizes the chemical synthesis of a conducting nanocomposite based on the incorporation of gold nanoparticles (Au) into the redox matrix of polyindole (PIn) along with the subsequent improvement in the overall properties of the composite by the addition of sulfonated graphene oxide (SGO). The bioanode was developed by the deposition of the PIn-Au-SGO nanocomposite with subsequent immobilization of ferritin (Frt) and glucose oxidase (GOx) on the glassy carbon electrode (GC). The successful application of the PIn-Au-SGO nanocomposite toward the development of a ferritin-mediated glucose biofuel cell anode was studied by the electrochemical characterization of the constructed bioanode (GC-PIn-Au-SGO/Frt/GOx) for the bioelectrocatalytic oxidation of glucose. The maximum current density obtained by the modified bioanode was found to be 17.8 mA cm-2 at the limiting glucose concentration of 50 mM in 0.1 M K4Fe(CN)6 at a scan rate of 100 mVs-1. The lifetime of the concerned bioelectrode when stored at 4 °C was estimated to be 53 days approximately. The appreciable results of the structural and electrochemical characterization of the PIn-Au-SGO based bioelectrode reveal its potential applications exclusively in implantable medical devices.

Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities.

A new series of phenolic glycoside esters, saccharumoside-B and its analogs (9b-9n, 10) have been synthesized by the Koenigs-Knorr reaction. Antiproliferative activities of the compounds (9b-9n, 10) were evaluated on various cancer cell lines including, MCF-7 breast, HL-60 leukemia, MIA PaCa-2 pancreatic, DU145 prostate, HeLa cervical and CaCo-2 colon, as well as normal human MCF10A mammary epithelial and human peripheral blood mononuclear cells (PBMC) by MTT assay. Compounds (9b-9n, 10) exhibited considerable antiproliferative effects against cancer cells with IC50 range of 4.43 ± 0.35 to 49.63 ± 3.59 µM, but they are less cytotoxic on normal cells (IC50 > 100 µM). Among all the compounds, 9f showed substantial antiproliferative activity against MCF-7 and HL-60 cells with IC50 of 6.13 ± 0.64 and 4.43 ± 0.35, respectively. Further mechanistic studies of 9f were carried out on MCF-7 and HL-60 cell lines. 9f caused arrest of cell cycle of MCF-7 and HL-60 cells at G0/G1 phase. Apoptotic population elevation, mitochondrial membrane potential loss, increase of cytosolic cytochrome c and Bax levels, decrease of Bcl-2 levels and enhanced caspases-9 and -3 activities were observed in 9f-treated MCF-7 and HL-60 cells. These results demonstrate anticancer and apoptosis-inducing potentials of 9f in MCF-7 and HL-60 cells via intrinsic pathway.

Photocatalytic degradation of Aniline from aqueous solutions under sunlight illumination using immobilized Cr:ZnO nanoparticles.

The present study aimed at synthesizing chromium doped zinc oxide nanoparticles (Cr:ZnO NPs) under mild hydrothermal conditions (temperature ~100 °C, p = autogenous and time ~12 hr). Chromium oxide and n-butylamine were used as dopant and surface modifier, respectively. The characteristics of the synthesized nanoparticles were determined through conducting specialized experiments including powder XRD, FTIR, SEM, EDX, and UV-VIS spectroscopy. Then, the Cr:ZnO NPs were immobilized on a sandblasted glass through thermal method. The photocatalytic degradation of aniline was conducted in a continuous reactor with a volume of 1.5 liters. Before and after photocatalytic degradation, the immobilized Cr:ZnO NPs were characterized for SEM and EDX to determine the degree of stability of immobilized nanoparticles as well as the influence of the current applied on them. The photodegradation operational parameters investigated were aniline initial concentration (150, 200, and 250 mg/L), pH (5, 7, 6, and 12), and reaction time (2, 4, and 6 hours) under sunlight illumination. The characterization results indicated high purity of the Cr:ZnO NPs and no change in morphology or composition even after the immobilization and photo-oxidation process. Finally, it was found that the optimum conditions for 93% removal of aniline under sunlight illumination was about 6 hours retention time at pH 9.

Nanotechnology for Alzheimer Disease.

BACKGROUND: Alzheimer disease (AD) typically affects behavior, memory and thinking. The change in brain have been reported to begin approx. 10-20 years before the appearance of actual symptoms and diagnosis of AD. An early stage diagnosis and treatment of this lethal disease is the prime challenge, which is mainly halted by the lack of validated biomarkers. METHOD: Recent nanotechnological advancements have the potential to offer large scale effective diagnostic and therapeutic options. Targeted drug (e.g. Rivastigmine) delivery with the help of nanoparticles (NPs) in the range of 1-100 nm diameters can effectively cross the blood brain barrier with minimized side effects. Moreover, biocompatible nanomaterials with increased magnetic and optical properties can act as excellent alternative agents for an early diagnosis. With the high volume of research coming in support of the effective usage of NP based drug delivery in critical environment of CNS, it is quite likely that this approach can end up providing remarkable breakthroughs in early stage diagnosis and therapy of AD. CONCLUSION: In the current review, we have presented a comprehensive outlook on the current challenges in diagnosis and therapy of AD, with an emphasis on the effective options provided by biocompatible NPs as imaging contrast agents and drug carriers.

Beyond mitochondria, what would be the energy source of the cell?

Currently, cell biology is based on glucose as the main source of energy. Cellular bioenergetic pathways have become unnecessarily complex in their eagerness to explain that how the cell is able to generate and use energy from the oxidation of glucose, where mitochondria play an important role through oxidative phosphorylation. During a descriptive study about the three leading causes of blindness in the world, the ability of melanin to transform light energy into chemical energy through the dissociation of water molecule was unraveled. Initially, during 2 or 3 years; we tried to link together our findings with the widely accepted metabolic pathways already described in metabolic pathway databases, which have been developed to collect and organize the current knowledge on metabolism scattered across a multitude of scientific articles. However, firstly, the literature on metabolism is extensive but rarely conclusive evidence is available, and secondly, one would expect these databases to contain largely the same information, but the contrary is true. For the apparently well studied metabolic process Krebs cycle, which was described as early as 1937 and is found in nearly every biology and chemistry curriculum, there is a considerable disagreement between at least five databases. Of the nearly 7000 reactions contained jointly by these five databases, only 199 are described in the same way in all the five databases. Thus to try to integrate chemical energy from melanin with the supposedly well-known bioenergetic pathways is easier said than done; and the lack of consensus about metabolic network constitutes an insurmountable barrier. After years of unsuccessful results, we finally realized that the chemical energy released through the dissociation of water molecule by melanin represents over 90% of cell energy requirements. These findings reveal a new aspect of cell biology, as glucose and ATP have biological functions related mainly to biomass and not so much with energy. Our finding about the unexpected intrinsic property of melanin to transform photon energy into chemical energy through the dissociation of water molecule, a role performed supposedly only by chlorophyll in plants, seriously questions the sacrosanct role of glucose and thereby mitochondria as the primary source of energy and power for the cells.