Neurodegenerative diseases (ND) remains to be one of the biggest burdens on healthcare systems and serves as a leading cause of disability and death. Alzheimer’s disease (AD) is among the most common of such disorders, followed by Parkinson’s disease (PD). The basic molecular details of disease initiation and pathology are still under research. Only recently, the role of exosomes has been linked to the initiation and progression of these neurodegenerative diseases. Exosomes are small bilipid layer enclosed extracellular vesicles, which were once considered as a cellular waste and functionless. These nano-vesicles of 30–150 nm in diameter carry specific proteins, lipids, functional mRNAs, and high amounts of non-coding RNAs (miRNAs, lncRNAs, and circRNAs). As the exosomes content is known to vary as per their originating and recipient cells, these vesicles can be utilized as a diagnostic biomarker for early disease detection. Here we review exosomes, their biogenesis, composition, and role in neurodegenerative diseases. We have also provided details for their characterization through an array of available techniques. Their updated role in neurodegenerative disease pathology is also discussed. Finally, we have shed light on a novel field of salivary exosomes as a potential candidate for early diagnosis in neurodegenerative diseases and compared the biomarkers of salivary exosomes with other blood/cerebrospinal fluid (CSF) based exosomes within these neurological ailments.
Autophagy, a catabolic process, degrades damaged and defective cellular materials through lysosomes, thus working as a recycling mechanism of the cell. It is an evolutionarily conserved and highly regulated process that plays an important role in maintaining cellular homeostasis. Autophagy is constitutively active at the basal level; however, it gets enhanced to meet cellular needs in various stress conditions. The process involves various autophagy-related genes that ultimately lead to the degradation of targeted cytosolic substrates. Many factors modulate both upstream and downstream autophagy pathways like nutritional status, energy level, growth factors, hypoxic conditions, and localization of p53. Any problem in executing autophagy can lead to various pathological conditions including neurodegeneration, aging, and cancer. In cancer, autophagy plays a contradictory role; it inhibits the formation of tumors, whereas, during advanced stages, autophagy promotes tumor progression. Besides, autophagy protects the tumor from various therapies by providing recycled nutrition and energy to the tumor cells. Autophagy is stimulated by tumor suppressor proteins, whereas it gets inhibited by oncogenes. Due to its dynamic and dual role in the pathogenesis of cancer, autophagy provides promising opportunities in developing novel and effective cancer therapies along with managing chemoresistant cancers. In this article, we summarize different strategies that can modulate autophagy in cancer to overcome the major obstacle, i.e., resistance developed in cancer to anticancer therapies.
The present study was conducted to determine the prognostic significance of I655V SNP (rs1136201) is a genetic one in HER-2 oncoprotein in cases of colorectal cancer (CRC). We conducted a case-control study analysing 83 subjects (naïve primary CRC cases) who underwent CRC biopsy/colectomy and included 57 healthy control subjects. Analysis of HER-2 polymorphism was done by PCR-RFLP technique. The mean age was found to be 55.9 years; median age was 56 years and mode age was 54 years with a range of 43 (30-73). Males constitute 63 (75.9%) and females constitute 20 (24.1%) of patient population. According to gradewise distribution, 12 (14.45%) patients were of Grade I, 53 (63.85%) of Grade II, and 18 (21.68%) were of Grade III. We found out that out of 83 patients, 52 (62.65%) were of homozygous wild type (A/A; Ile/ Ile); 27 (32.53%) were of heterozygous type (A/G; Ile/Val) and 4 (4.81%) were of homozygous mutant type (G/G; Val/Val). Allelic frequency of Ile (A) was found out to be 0.79 and that of Val (G) is 0.21 and were not significantly different from the healthy control population. Fischer's exact p value obtained was 0.86.
Parkinson’s disease is generally asymptomatic at earlier stages. The pressing need is for the susceptibility risk biomarkers, that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of exosomes in progression of neurodegenerative diseases is already reported and its cargo could be potent in playing a revolutionary role in biomarker discovery. In our study, the salivary exosomes were efficiently isolated by chemical precipitation from subjects (PD = 70, healthy controls = 26 and probable PD = 08) followed by antibody-based validation through CD63, CD9, GAPDH, flotillin 1, L1CAM, and calnexin. Morphological characterization of the isolated exosomes through transmission elcetrom microscopy (TEM). The exosome quantification via fluorescence and antibody-based nanoparticle tracking analysis (NTA). The total alpha-synuclein (α-syntotal) in salivary exosomal cargo was quantified by ELISA. The disease severity staging confirmation was done by 99mTc-TRODAT-SPECT. We observed a significant increase in total exosome concentration in PD patients than the healthy control (HC) where fluorescence-tagged exosomes were observed to be higher in PD (p < 0.0001) than the HC using NTA with a sensitivity of 94.34%. This results was validated through exosomes tagged with antibody CD63 (p = 0.006) with a similar sensitivity of 94.12%. We further validated our findings with the ELISA-based α-syntotal concentration in exosomes where it was observed to be higher in PD with a sensitivity of 88.24%. The striatal binding ratios in 99mTc-TRODAT-SPECT shown positive correlation with fluorescent exosomes concentration r = 0.3000, α-syntotal concentration r = 0.8000. In this study for the first time we have found that the fluorescence tagged exosomes has potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.
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