Title:The Derivatives of Cromolyn Ameliorate the Abnormal Misfolding of
Amyloid Proteins and Neuroinflammation in the Neural Cells
Volume: 30
Issue: 39
Author(s): Joo-Hee Lee, Nivethasri Lakshmana Perumal, Sehee Kwon, Hee-Cheol Kim, Na-Hyun Ahn, Su-Bin Choi, Eunjin Hwang, Hyoryeong Song, David R. Elmaleh, Aryun Kim, Woong-Suk Yang, Cheorl-Ho Kim*, Byeong-Churl Jang*, Sungwoon Choi*Seung-Hoon Yang*
Affiliation:
- Department of Biological Sciences, Sungkyunkwan University and Samsung Advanced Institute of Health Science
and Technology, Suwon, 16419, Republic of Korea
- Department of Molecular
Medicine, Keimyung University, Daegu, 42601, Republic of Korea
- Department of New Drug Discovery, Chungnam National University, Daejeon,
34134, Republic of Korea
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Republic of Korea
Keywords:
Alzheimer's Disease, cromolyn sodium, derivate, beta-amyloid (1-42), tau proteins, neuroinflammation.
Abstract:
Background: The representative symptom of Alzheimer’s Disease (AD) has
mainly been mentioned to be misfolding of amyloid proteins, such as amyloid-beta (Aβ)
and tau protein. In addition, the neurological pathology related to neuroinflammatory signaling
has recently been raised as an important feature in AD. Currently, numerous drug
candidates continue to be investigated to reduce symptoms of AD, including amyloid proteins
misfolding and neuroinflammation.
Objective: Our research aimed to identify the anti-AD effects of two chemical derivatives
modified from cromoglicic acid, CNU 010 and CNU 011.
Methods: CNU 010 and CNU 011 derived from cromoglicic acid were synthesized. The
inhibitory effects of Aβ and tau were identified by thioflavin T assay. Moreover, western
blots were conducted with derivates CNU 010 and CNU 011 to confirm the effects on inflammation.
Results: CNU 010 and CNU 011 significantly inhibited the aggregation of Aβ and tau
proteins. Moreover, they reduced the expression levels of mitogen-activated protein
(MAP) kinase and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-
κB) signaling proteins, which are representative early inflammatory signaling markers.
Also, the inhibitory effects on the lipopolysaccharide (LPS)-induced cyclooxygenase
(COX)-2 and inducible nitric oxide synthase (iNOS) expression referring to late inflammation
were confirmed.
Conclusion: Our results showing multiple beneficial effects of cromolyn derivatives
against abnormal aggregation of amyloid proteins and neuroinflammatory signaling provide
evidence that CNU 010 and CNU 011 could be further developed as potential drug
candidates for AD treatment.
