ADAMTS4, 5, 9, and 15 Expressions in the Autopsied Brain of Patients with Alzheimer's Disease: A Preliminary Immunohistochemistry Study

Pehlivan, Sultan; Fedakar, Recep; Eren, Bülent; Akyol, Sümeyya; Eren, Filiz; İnanır, Nursel Türkmen; Gürses, Murat Serdar; Ural, Mustafa; Tağıl, Süleyman Murat; Demircan, Kadir

doi:10.5455/bcp.20150706034008

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…ADAMTS expression was discovered in the central nervous system (CNS) after various extensive research and is known to change in disease circumstances ( Miguel, Pollak & Lubec, 2005 ; Haddock et al, 2006 ; Gottschall & Howell, 2015 ). The downregulation of ADAMTS5 expression level in our A β group data was supported by previous study which demonstrated that ADAMTS4 and ADAMTS5 expressions were slightly under-expressed in case of AD which indicated the deficiency in the elimination of ECM in patients, which ultimately resulted in the accumulation of undesirable ECM compounds over time ( Pehlivan et al, 2016 ). Likewise, increase expression of ADAMTS5 from the combined treatment may assist in elevating the deterioration of ECM constituents, including A β senile plaque ( Pekny & Nilsson, 2005 ), which in turn, might aid recovery by the elimination of the CSPGs.…”

Section: Discussionsupporting

confidence: 85%

Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (Aβ) explicit pathway: recovery and reversal paradigm effects

Manap

Madhavan

Vijayabalan

et al. 2020

PeerJ

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Previously, we reported the synergistic effects of curcumin and piperine in cell cultures as potential anti-cholinesterase and anti-amyloidogenic agents. Due to limited findings on the enrolment of these compounds on epigenetic events in AD, we aimed at elucidating the expression profiles of Aβ42-induced SH-SY5Y cells using microarray profiling. In this study, an optimized concentration of 35 µM of curcumin and piperine in combination was used to treat Aβ42 fibril and high-throughput microarray profiling was performed on the extracted RNA. This was then compared to curcumin and piperine used singularly at 49.11 µM and 25 µM, respectively. Our results demonstrated that in the curcumin treated group, from the top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p < 0.05; fold change ≥ 2 or ≤ −2), there were five upregulated and three downregulated genes involved in the amyloidogenic pathway. While from top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p < 0.05; fold change ≥ 2 or ≤ − 2) in the piperine treated group, there were four upregulated and three downregulated genes involved in the same pathway, whereas there were five upregulated and two downregulated genes involved (p < 0.05; fold change ≥ 2 or ≤ − 2) in the curcumin-piperine combined group. Four genes namely GABARAPL1, CTSB, RAB5 and AK5 were expressed significantly in all groups. Other genes such as ITPR1, GSK3B, PPP3CC, ERN1, APH1A, CYCS and CALM2 were novel putative genes that are involved in the pathogenesis of AD. We revealed that curcumin and piperine have displayed their actions against Aβ via the modulation of various mechanistic pathways. Alterations in expression profiles of genes in the neuronal cell model may explain Aβ pathology post-treatment and provide new insights for remedial approaches of a combined treatment using curcumin and piperine.

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Section: Discussionsupporting

confidence: 85%

Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (Aβ) explicit pathway: recovery and reversal paradigm effects

Manap

Madhavan

Vijayabalan

et al. 2020

PeerJ

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“…This finding may represent specific marker for the diagnosis of AD, and for the treatment of AD. Pehlivan et al [76] demonstrates that ADAMTS4 and 5 is slightly under-expressed in the brains from autopsied AD cases compared to control brains and suggests that ECM degradation is not promoted in AD brain. On the other hand, ADAMTS9 and 15 aggrecanases were not found to be expressed in brain sections of AD and control cases.…”

Section: The Possible Functions Of Adamts Proteases In Admentioning

confidence: 99%

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

Gürses¹,

Ural²,

Güleç³

et al. 2016

Aging and disease

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The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals.Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer's disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.

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“…Thus, Sato and colleagues [105] demonstrated that ADAMTS4 mRNA is induced by Aβ-treatment, suggesting a crucial role in AD progression. Additionally, investigation on human post-mortem brains of AD patients yielded reduced protein amounts of ADAMTS4 and 5, and complete absence of ADAMTS9, pointing to a malfunction of PN component degradation [106].…”

Section: Discussionmentioning

confidence: 99%

Tau Protein Modulates Perineuronal Extracellular Matrix Expression in the TauP301L-acan Mouse Model

et al. 2022

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Tau mutations promote the formation of tau oligomers and filaments, which are neuropathological signs of several tau-associated dementias. Types of neurons in the CNS are spared of tau pathology and are surrounded by a specialized form of extracellular matrix; called perineuronal nets (PNs). Aggrecan, the major PN proteoglycans, is suggested to mediate PNs neuroprotective function by forming an external shield preventing the internalization of misfolded tau. We recently demonstrated a correlation between aggrecan amount and the expression and phosphorylation of tau in a TauP310L-acan mouse model, generated by crossbreeding heterozygous aggrecan mice with a significant reduction of aggrecan and homozygous TauP301L mice. Neurodegenerative processes have been associated with changes of PN structure and protein signature. In this study, we hypothesized that the structure and protein expression of PNs in this TauP310L-acan mouse is regulated by tau. Immunohistochemical and biochemical analyses demonstrate that protein levels of PN components differ between TauP301LHET-acanWT and TauP301LHET-acanHET mice, accompanied by changes in the expression of protein phosphatase 2 A. In addition, tau can modulate PN components such as brevican. Co-immunoprecipitation experiments revealed a physical connection between PN components and tau. These data demonstrate a complex, mutual interrelation of tau and the proteoglycans of the PN.

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ADAMTS4, 5, 9, and 15 Expressions in the Autopsied Brain of Patients with Alzheimer's Disease: A Preliminary Immunohistochemistry Study

Cited by 6 publications

References 36 publications

Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (Aβ) explicit pathway: recovery and reversal paradigm effects

Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (Aβ) explicit pathway: recovery and reversal paradigm effects

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease

Tau Protein Modulates Perineuronal Extracellular Matrix Expression in the TauP301L-acan Mouse Model

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