19 research outputs found
Thrombospondin-1 protects against Aฮฒ-induced mitochondrial fragmentation and dysfunction in hippocampal cells.
Alzheimer's disease (AD) is often characterized by the impairment of mitochondrial function caused by excessive mitochondrial fragmentation. Thrombospondin-1 (TSP-1), which is primarily secreted from astrocytes in the central nervous system (CNS), has been suggested to play a role in synaptogenesis, spine morphology, and synaptic density of neurons. In this study, we investigate the protective role of TSP-1 in the recovery of mitochondrial morphology and function in amyloid ฮฒ (Aฮฒ)-treated mouse hippocampal neuroblastoma cells (HT22). We observe that TSP-1 inhibits Aฮฒ-induced mitochondrial fission by maintaining phosphorylated-Drp1 (p-Drp1) levels, which results in reduced Drp1 translocation to the mitochondria. By using gabapentin, a drug that antagonizes the interaction between TSP-1 and its neuronal receptor ฮฑ2ฮด1, we observe that ฮฑ2ฮด1 acts as one of the target receptors for TSP-1, and blocks the reduction of the p-Drp1 to Drp1 ratio, in the presence of Aฮฒ. Taken together, TSP-1 appears to contribute to maintaining the balance in mitochondrial dynamics and mitochondrial functions, which is crucial for neuronal cell viability. These data suggest that TSP-1 may be a potential therapeutic target for AD
Inactivation of Medial Prefrontal Cortex Impairs Time Interval Discrimination in Rats
Several lines of evidence suggest the involvement of prefrontal cortex in time interval estimation. The underlying neural processes are poorly understood, however, in part because of the paucity of physiological studies. The goal of this study was to establish an interval timing task for physiological recordings in rats, and test the requirement of intact medial prefrontal cortex (mPFC) for performing the task. We established a temporal bisection procedure using six different time intervals ranging from 3018 to 4784โms that needed to be discriminated as either long or short. Bilateral infusions of muscimol (GABAA receptor agonist) into the mPFC significantly impaired animal's performance in this task, even when the animals were required to discriminate between only the longest and shortest time intervals. These results show the requirement of intact mPFC in rats for time interval discrimination in the range of a few seconds
Genetic associations of in vivo pathology influence Alzheimers disease susceptibility
Introduction
Although the heritability of sporadic Alzheimers disease (AD) is estimated to be 60โ80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques.
Methods
Targeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using 11C-Pittsburgh Compound B positron emission tomography (PET), 18F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimers disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups.
Results
We called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid ฮฒ (Aฮฒ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF)โ>โ0.05) yielded several novel loci associated with Aฮฒ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AFโ<โ0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features.
Conclusions
This study provides novel associations of genetic factors to Aฮฒ accumulation and AD-related neurodegeneration to influence AD susceptibility.The study was supported by grants from the National Research Foundation of Korea (2014M3C7A1046049 and 2018M3C9A5064708 for Choi M and 2014M3C7A1046042 for Lee DY) and grants from the Ministry of Health and Welfare of Korea (HI18C0630 for Mook-Jung IH and Lee DY, and HI19C0149 for Lee DY)
Mitochondria-Specific Accumulation of Amyloid ฮฒ Induces Mitochondrial Dysfunction Leading to Apoptotic Cell Death
Mitochondria are best known as the essential intracellular organelles that host the homeostasis required for cellular survival, but they also have relevance in diverse disease-related conditions, including Alzheimer's disease (AD). Amyloid ฮฒ (Aฮฒ) peptide is the key molecule in AD pathogenesis, and has been highlighted in the implication of mitochondrial abnormality during the disease progress. Neuronal exposure to Aฮฒ impairs mitochondrial dynamics and function. Furthermore, mitochondrial Aฮฒ accumulation has been detected in the AD brain. However, the underlying mechanism of how Aฮฒ affects mitochondrial function remains uncertain, and it is questionable whether mitochondrial Aฮฒ accumulation followed by mitochondrial dysfunction leads directly to neuronal toxicity. This study demonstrated that an exogenous Aฮฒ1โ42 treatment, when applied to the hippocampal cell line of mice (specifically HT22 cells), caused a deleterious alteration in mitochondria in both morphology and function. A clathrin-mediated endocytosis blocker rescued the exogenous Aฮฒ1โ42-mediated mitochondrial dysfunction. Furthermore, the mitochondria-targeted accumulation of Aฮฒ1โ42 in HT22 cells using Aฮฒ1โ42 with a mitochondria-targeting sequence induced the identical morphological alteration of mitochondria as that observed in the APP/PS AD mouse model and exogenous Aฮฒ1โ42-treated HT22 cells. In addition, subsequent mitochondrial dysfunctions were demonstrated in the mitochondria-specific Aฮฒ1โ42 accumulation model, which proved indistinguishable from the mitochondrial impairment induced by exogenous Aฮฒ1โ42-treated HT22 cells. Finally, cellular toxicity was directly induced by mitochondria-targeted Aฮฒ1โ42 accumulation, which mimics the apoptosis process in exogenous Aฮฒ1โ42-treated HT22 cells. Taken together, these results indicate that mitochondria-targeted Aฮฒ1โ42 accumulation is the necessary and sufficient condition for Aฮฒ-mediated mitochondria impairments, and leads directly to cellular death rather than along with other Aฮฒ-mediated signaling alterations
Investigating the mechanism of Aฮฒ-induced mitochondrial dysfunctiion as a risk factor for Alzheimer's disease
ํ์๋
ผ๋ฌธ (๋ฐ์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ : ์๊ณผ๋ํ ์๊ณผํ๊ณผ ์๊ณผํ์ ๊ณต, 2016. 2. ๋ฌต์ธํฌ.์์ธ ํ์ด๋จธ๋ณ์ ๊ฐ์ฅ ํฐ ํน์ง์ ์ธํฌ ์ธ๋ถ์ ๋ฒ ํ-์๋ฐ๋ก์ด๋ (Aฮฒ) ํ๋ผํฌ์ ์ถ์ ๊ณผ ์ธํฌ ๋ด๋ถ์ ๊ณผ์ธ์ฐํ๋ ํ์ฐ ๋จ๋ฐฑ์ง์ ๋น์ ์์ ์ธ ์ ํ ํ์์ ๋ค ์ ์๋๋ฐ, ์ต๊ทผ ์ด๋ฌํ ํ์ํ์ ์ธ ์ธํฌ ๋ณํ ๋ฟ๋ง ์๋๋ผ ๊ทธ์ ์ํด ์ํฅ์ ๋ฐ๋ ์๋ฆฌ์ ๊ธฐ๋ฅ์ ์ด์์ด๋ ์ธํฌ ์๊ธฐ๊ด์ ๊ธฐ๋ฅ์ ๊ฒฐํจ๋ค์ด ์ง์ ์ ์ธ ๋ณ์ธ ๊ธฐ์ ์ผ๋ก์จ ๋ง์ ์ฐ๊ตฌ๊ฐ ๋๊ณ ์๋ค. ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ ์ด์๊ณผ autophagosome์ ์ถ์ ๋ ๊ทธ๋ค ์ค ํ๋์ด๋ค. ํ์ง๋ง ์์ง๊น์ง ์ด์ ๋ํ ๋๋ ทํ ๋ฉ์ปค๋์ฆ์ด ๋ฐํ์ง ๋ฐ๊ฐ ์๊ธฐ์, ๋ณธ ์ฐ๊ตฌ์์๋ ์ด๋ฅผ ๊ตฌ์ฒด์ ์ผ๋ก ๋ฐํ๊ณ ์ ํ์๋ค.
๋จผ์ , Crif1 (CR6 interacting factor 1) ์ด๋ผ๋ ๋จ๋ฐฑ์ง์ด ์์ธ ํ์ด๋จธ๋ณ ๋๋ฌผ๋ชจ๋ธ๊ณผ ํ์์์ ๊ฐ์๋์ด ์์์ ๊ด์ฐฐํ์ฌ SY5Y ์ธํฌ์ฃผ์์ Aฮฒ์ ์ํด ๊ฐ์๋ Crif1์ ์์ ํ๋ณต์์ผ ์ฃผ์๊ณ ์ด๋ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ๊ณผ ๋ชจ์, ์ธํฌ์ ํ์ฑ ๋ฑ์ด ์ ์์ ์ผ๋ก ํ๋ณต๋จ์ ํตํด Crif1์ด ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ ์ ์ง๋ฅผ ์ํ ์ค์ ๋จ๋ฐฑ์ง์์ธ ๋์์ ์์ธ ํ์ด๋จธ๋ณ์์ ์ฃผ์ ์น๋ฃ ํ์ ์ผ๋ก ๊ธฐ๋ฅํ ์ ์์์ ๋ฐํ๋ด์๋ค. ๋ํ, ๋์ ์ฑ์์ธํฌ (astrocyte) ์์ ์ฃผ๋ก ๋ถ๋น๋์ด ์ ๊ฒฝ์ธํฌ์ ์์ฉํ๋ค๊ณ ์๋ ค์ ธ ์๋ Tsp-1 (Thrombospondin-1) ์ ์์ธ ํ์ด๋จธ๋ณ ํ์์ ๋๋ฌผ ๋ชจ๋ธ์์ ๊ทธ ์์ด ๊ฐ์๋์ด ์๋๋ฐ, ๋ณธ ์ฐ๊ตฌ์์ Tsp-1์ด Aฮฒ์ ์ํ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ณผ๋ถ์ด ํ์์ ์ ํดํด ๊ทธ์ ๋ฐ๋ฅธ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ ์ด์ ๋ฐ ์ธํฌ ํ์ฑ์ ๋ณดํธ ํจ๊ณผ๋ฅผ ๋ผ ์ ์์์ ํ์ธํ์๋ค. ์ด๋ก์จ Tsp1 ๋ํ ์์ธ ํ์ด๋จธ๋ณ ์ํฉ์์ ๋ฏธํ ์ฝ๋๋ฆฌ์์์ ๋ณดํธ ํจ๊ณผ๋ฅผ ๋์ผ๋ก์จ ์ข์ ์น๋ฃ ํ์ ์ด ๋ ์ ์์์ ํ์ธํ์๋ค.
์์ธ ํ์ด๋จธ๋ณ์ ์ 3์ ๋น๋จ๋ณ์ด๋ผ๊ณ ๋ถ๋ฆฌ์ด์ง ๋งํผ ๋น๋จ๋ณ๊ณผ์ ์ฐ๊ด์ฑ์ด ๊น์ ๊ฒ์ผ๋ก๋ ์๋ ค์ ธ ์๋ค. ๋ณธ ์ฐ๊ตฌ์์๋ ์ 2ํ ๋น๋จ๋ณ ์น๋ฃ์ ๋ก ๊ฐ์ฅ ํํ ์ฐ์ด๋ metformin์ด ์์ธ ํ์ด๋จธ๋ณ ํ์์ ๋๋ฌผ ๋ชจ๋ธ์์ Aฮฒ ์์ฑ์ ์ฆ๊ฐ์ํด์ ํ์ธํ๊ณ , HT22 ์ธํฌ์ฃผ์์ metformin์ด ์์ธ ํ์ด๋จธ๋ณ์ ์ฃผ์ ๋ณ์ธ ๊ธฐ์ ์ค์ ํ๋์ธ autophagosome์ ์ถ์ ์ ์ ๋ํ์ฌ Aฮฒ ์์ฑ ์ฆ๊ฐ์ ๊ธฐ์ฌํ ์ ์์์ ํ์ธํ์๋ค.
๋ณธ ์ฐ๊ตฌ๋ฅผ ํตํด, ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ตฌ์กฐ์ , ๊ธฐ๋ฅ์ ์ ์ํ๊ฐ ์์ธ ํ์ด๋จธ๋ณ์์ ์ค์ํ ์น๋ฃ ์ ๋ต์ด ๋ ์ ์์์ ๋ฐํ๋๊ณผ ๋์์, metformin์ด๋ผ๋ ์ 2ํ ๋น๋จ๋ณ ์น๋ฃ์ ๊ฐ ๊ทธ ๋ณ์ฆ์ ๊ฐ์ํ์ํฌ ์ ์๋ ๊ฐ๋ฅ์ฑ์ ๋ํด ์ ์ํ ์ ์์๋ค.Alzheimers disease (AD), a devastating form of dementia is the most common-age related neurological disorder. Extracellular Aฮฒ accumulation and abnormal folding of intracellular hyper-phosphorylated tau proteins are two hall-marks of Alzheimers disease pathology. Recently, many studies have been focused on the maintenance of essential and principal physiological functions or the functional recovery of cellular organelles functions to increase the cell viability. Since mitochondrial dysfunction and accumnulation of autophagosomes are one of them, this study tried to reveal the mechanisms underlying between those risk factors and AD pathology progression. We found out that Aฮฒ-induced disruption of mitochondrial morphology and function is mainly caused by Crif1 (CR6-interacting factor 1) loss. Furthermore, since Crif1 over-expression could recover Aฮฒ-induced mitochondrial dysfunction, mitochondrial morphology disruption and decrease of cell viability in SH-SY5Y cells, Crif1 might be the good therapeutic target for AD maintaining mitochondrial functions. In addition, this study additionally confirmed that Tsp1 (Thrombospondin-1), which is released from astrocytes in CNS, appears to protect mitochondrial morphology and functions by inhibiting Aฮฒ-induced calcium mediated calcineurin activation and following decrease of p-Drp1 level, which also can be a potential therapeutic strategy for AD.
The association between type 2 diabetes and AD has been known to be quite strong. This study revealed the effect of metformin in Aฮฒ production by showing that metformin accumulates autophagosomes where amyloidogenic APP processing is facilitated in HT22 cells.
Based on these results, it is highly possible that maintaining mitochondrial function might be a good therapeutic approach in treating AD. Furthermore, this study also warns us for the effect of metformin that might contribute to AD pathology by enhancing Aฮฒ generation.์๋ก 1
Part 1. ์์ธ ํ์ด๋จธ๋ณ์์ ๊ด์ฐฐ๋๋ Crif1 ๋จ๋ฐฑ์ง์ ๊ฐ์๋ก ์ด๋๋๋ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ ์ ํด ์ฐ๊ตฌ 3
Part 2. Tsp-1์ A์ ์ํ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ตฌ์กฐ ๋ง๊ฐ์ง ๋ฐ ๊ธฐ๋ฅ ์ด์์์ ํ๋ณต ๊ธฐ์ ์ฐ๊ตฌ 4
Part 3. Metformin์ ์ํ A ์์ฑ ์ฆ๊ฐ ๋ฉ์ปค๋์ฆ์ ๋ํ ์ฐ๊ตฌ 5
์คํ์ฌ๋ฃ ๋ฐ ๋ฐฉ๋ฒ 17
1. ์คํ์ ์ด์ฉ๋ ์คํ๋๋ฌผ 17
2. ์ 2ํ ๋น๋จ๋ณ ์น๋ฃ์ ์ธ metforminํฌ์ฌ ๋ฐฉ๋ฒ 18
3. ์ธํฌ์ฃผ ๋ฐ ์ธํฌ๋ฐฐ์ (Cell line and Cell culture) 18
4. ์์ฝ (Reagents) 19
5. ํ๋ผ์ค๋ฏธ๋ DNA ๋ฐ siRNA ํ์ง์ฃผ์
(Transfection) 19
6. ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ ๋ถ์ 20
7. ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๋ชจ์ ๋ถ์ 21
8. ์จ์คํด ๋ธ๋กฏ (Western Blot) 22
9. ์ธํฌ ํ์ฑ ๋ถ์ ์คํ 24
10. RNA ๋ถ๋ฆฌ์ ์ญ์ ์ฌ ์คํฉ์ฐ์ํจ์๋ฐ์ (RT-PCR) 26
11. ์ ๋์ ์ค์๊ฐ ์คํฉ์ฐ์ํจ์๋ฐ์ (qRT-PCR) 26
12. ์ ๊ธฐ์ด๋ ๊ธฐ๋์ฑ ๊ต๋ ์คํ (EMSA) 27
13. ๋ฉด์ญ์นจ๊ฐ๋ฒ (Immunoprecipitation) 27
14. ๋ฉด์ญ์กฐ์ง์ผ์ (Immunohistochemistry) 28
15. ์ธํฌ ๋ด ์นผ์ ์ธก์ 29
16. Luciferase reporter gene assay 30
17. BACE1 promoter activity assay 30
18. A ELISA assay 31
19. Trichloroacetic acid (TCA) precipitation 32
20. ์ ์ํ๋ฏธ๊ฒฝ ๊ด์ฐฐ 32
21. Microsome enriched crude fraction ๋ถ๋ฆฌ 33
22. In vitro peptide cleavage assay 34
23. A1-42 ์ค๋น (A1-42 preparation) 35
24. ํต๊ณ์ฒ๋ฆฌ 35
๊ฒฐ๊ณผ 36
Part 1. A์ ์ํ Crif1 ๋จ๋ฐฑ์ง์ ๊ฐ์๋ก ์ด๋๋๋ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ ์ ํด ์ฐ๊ตฌ 36
1. 5XFAD ์ฅ์ ์์ธ ํ์ด๋จธ๋ณ ํ์์ ๋ณ๋ณ ์ง์ญ์์ ๋ณด์ด๋ Crif1 ๋จ๋ฐฑ์ง์ ์ ํ 36
2. A์ ์ํด ์ฆ๊ฐํ ROS๊ฐ Sp1์ ์ ์ฌ ํ์ฑ์ ๋ฏธ์น๋ ์ํฅ 38
3. ๋ฏธํ ์ฝ๋๋ฆฌ์ ๋ชจ์ ์ ์ง์ ์์ด์์ Crif1์ ์ญํ 40
4. Crif1์ ๊ฐ์๊ฐ ๋ฏธํ ์ฝ๋๋ฆฌ์ ๊ธฐ๋ฅ์ ๋ฏธ์น๋ ์ํฅ 42
5. A์ ์ํ ๋ฏธํ ์ฝ๋๋ฆฌ์ ๋ชจ์ ๋ง๊ฐ์ง๊ณผ ๊ธฐ๋ฅ ์ด์์ Crif1 ๊ณผ๋ฐํ์ด ๊ฐ์ง๋ ํ๋ณต ํจ๊ณผ 43
6. Crif1์ ์์ด A์ ์ํ ์ธํฌ ํ์ฑ ๊ฐ์์ ๋ฏธ์น๋ ์ํฅ 43
Part 2. Tsp1์ ์ํ ์์ธ ํ์ด๋จธ๋ณ์์์ ๋ฏธํ ์ฝ๋๋ฆฌ์ ๊ธฐ๋ฅ ์ด์ ํ๋ณต ์ฐ๊ตฌ 70
1. Tsp1์ด A์ ์ํ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ณผ๋ํ ๋ถ์ด์ ์ ํดํจ์ ํ์ธ 70
2. Tsp1์ด A์ ์ํ ๋ฏธํ ์ฝ๋๋ฆฌ์ ๊ธฐ๋ฅ ์ด์์ ์ ํดํจ์ ํ์ธ 71
3. Tsp1์ด A์ ์ํ ์ ๊ฒฝ ์ธํฌ์ฌ๋ฅผ ์ ํดํจ์ ํ์ธ 71
4. Tsp1์ด A์ ์ํ calcineurin ํ์ฑํ์ p-Drp1 ๋จ๋ฐฑ์ง์ ๊ฐ์๋ฅผ ์ ํดํจ์ ํ์ธ 72
Part 3. Metformin์ ์ํ A ์์ฑ ์ฆ๊ฐ ๋ฉ์ปค๋์ฆ์ ๋ํ ์ฐ๊ตฌ 83
1. 5XFAD ์ฅ์ ๋์์ metformin์ A ํ๋ผํฌ ํ์ฑ ์ฆ๊ฐ์ A42 ์์ฑ ์ฆ๊ฐ ํจ๊ณผ 83
2. Metformin์ด SH-SY5Y ์ธํฌ์์ ๋ฒ ํ-, ๊ฐ๋ง-์ํฌ๋ฆฌํ
์์ ์ ํ์ฑ์ ์ฆ๊ฐ์์ผ A๋ฅผ ์ฆ๊ฐ์ํด์ ํ์ธ 84
3. Metformin์ด SH-SY5Y์ธํฌ์์ autophagosome์ ์ถ์ ์ํด์ ํ์ธ 85
4. Metformin์ ์ํ autophagosome ์ฆ๊ฐ๋ AMPK ์ ํธ์ ๋ฌ ๊ฒฝ๋ก์ ์์กด์ ์์ ๊ท๋ช
86
๊ณ ์ฐฐ 96
Part 1. ์์ธ ํ์ด๋จธ๋ณ์์ ๊ด์ฐฐ๋๋ Crif1 ๋จ๋ฐฑ์ง์ ๊ฐ์๋ก ์ด๋๋๋ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ธฐ๋ฅ ์ ํด ์ฐ๊ตฌ 97
Part 2. Tsp1์ A์ ์ํ ๋ฏธํ ์ฝ๋๋ฆฌ์์ ๊ตฌ์กฐ ๋ง๊ฐ์ง๊ณผ ๊ธฐ๋ฅ ์ด์์์ ํ๋ณต ๊ธฐ์ ์ฐ๊ตฌ 102
Part 3. Metformin์ ์ํ A ์์ฑ ์ฆ๊ฐ ๋ฉ์ปค๋์ฆ์ ๋ํ ์ฐ๊ตฌ 106
๊ฒฐ๋ก 113
์ฐธ๊ณ ๋ฌธํ 116
Abstract 124Docto
Association of Angiotensin Converting Enzyme I/D and ฮฑ-actinin-3 R577X Genotypes with Growth Factors and Physical Fitness in Korean Children
Unmasking molecular profiles of bladder cancer
Precision medicine is designed to tailor treatments for individual patients by factoring in each person's specific biology and mechanism of disease. This paradigm shifted from a โone size fits allโ approach to โpersonalized and precision careโ requires multiple layers of molecular profiling of biomarkers for accurate diagnosis and prediction of treatment responses. Intensive studies are also being performed to understand the complex and dynamic molecular profiles of bladder cancer. These efforts involve looking bladder cancer mechanism at the multiple levels of the genome, epigenome, transcriptome, proteome, lipidome, metabolome etc. The aim of this short review is to outline the current technologies being used to investigate molecular profiles and discuss biomarker candidates that have been investigated as possible diagnostic and prognostic indicators of bladder cancer