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Article ; Online: Alzheimer's Disease: Challenges and a Therapeutic Opportunity to Treat It with a Neurotrophic Compound.

Baazaoui, Narjes / Iqbal, Khalid

2022 Volume 12, Issue 10

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease with an insidious onset and multifactorial nature. A deficit in neurogenesis and synaptic plasticity are considered the early pathological features associated with neurofibrillary tau ... ...

Abstract	Alzheimer's disease (AD) is a progressive neurodegenerative disease with an insidious onset and multifactorial nature. A deficit in neurogenesis and synaptic plasticity are considered the early pathological features associated with neurofibrillary tau and amyloid β pathologies and neuroinflammation. The imbalance of neurotrophic factors with an increase in FGF-2 level and a decrease in brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) in the hippocampus, frontal cortex and parietal cortex and disruption of the brain micro-environment are other characteristics of AD. Neurotrophic factors are crucial in neuronal differentiation, maturation, and survival. Several attempts to use neurotrophic factors to treat AD were made, but these trials were halted due to their blood-brain barrier (BBB) impermeability, short-half-life, and severe side effects. In the present review we mainly focus on the major etiopathology features of AD and the use of a small neurotrophic and neurogenic peptide mimetic compound; P021 that was discovered in our laboratory and was found to overcome the difficulties faced in the administration of the whole neurotrophic factor proteins. We describe pre-clinical studies on P021 and its potential as a therapeutic drug for AD and related neurodegenerative disorders. Our study is limited because it focuses only on P021 and the relevant literature; a more thorough investigation is required to review studies on various therapeutic approaches and potential drugs that are emerging in the AD field.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Brain-Derived Neurotrophic Factor ; Amyloid beta-Peptides/metabolism ; Neurodegenerative Diseases ; Fibroblast Growth Factor 2
Chemical Substances	Brain-Derived Neurotrophic Factor ; Amyloid beta-Peptides ; Fibroblast Growth Factor 2 (103107-01-3)
Language	English
Publishing date	2022-10-02
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12101409
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Article ; Online: COVID-19 and Neurodegenerative Diseases: Prion-Like Spread and Long-Term Consequences.

Baazaoui, Narjes / Iqbal, Khalid

Journal of Alzheimer's disease : JAD

2022 Volume 88, Issue 2, Page(s) 399–416

Abstract: COVID-19 emerged as a global pandemic starting from Wuhan in China and spread at a lightning speed to the rest of the world. One of the potential long-term outcomes that we speculate is the development of neurodegenerative diseases as a long-term ... ...

Abstract	COVID-19 emerged as a global pandemic starting from Wuhan in China and spread at a lightning speed to the rest of the world. One of the potential long-term outcomes that we speculate is the development of neurodegenerative diseases as a long-term consequence of SARS-CoV-2 especially in people that have developed severe neurological symptoms. Severe inflammatory reactions and aging are two very strong common links between neurodegenerative diseases and COVID-19. Thus, patients that have very high viral load may be at high risk of developing long-term adverse neurological consequences such as dementia. We hypothesize that people with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and aged people are at higher risk of getting the COVID-19 than normal adults. The basis of this hypothesis is the fact that SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 to enter the host cell and that this interaction is calcium-dependent. This could then suggest a direct relationship between neurodegenerative diseases, ACE-2 expression, and the susceptibility to COVID-19. The analysis of the available literature showed that COVID-19 virus is neurotropic and was found in the brains of patients infected with this virus. Furthermore, that the risk of having the infection increases with dementia and that infected people with severe symptoms could develop dementia as a long-term consequence. Dementia could be developed following the acceleration of the spread of prion-like proteins. In the present review we discuss current reports concerning the prevalence of COVID-19 in dementia patients, the individuals that are at high risk of suffering from dementia and the potential acceleration of prion-like proteins spread following SARS-CoV-2 infection.
MeSH term(s)	Aged ; COVID-19/epidemiology ; Dementia ; Humans ; Neurodegenerative Diseases/epidemiology ; Prions ; SARS-CoV-2
Chemical Substances	Prions
Language	English
Publishing date	2022-05-16
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-220105
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Article ; Online: Functional Characterization of

Ben Saad, Rania / Ben Romdhane, Walid / Baazaoui, Narjes / Bouteraa, Mohamed Taieb / Chouaibi, Yosra / Mnif, Wissem / Ben Hsouna, Anis / Kačániová, Miroslava

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Cold stress is a key environmental factor affecting plant growth and development, crop productivity, and geographic distribution. Thioredoxins (Trxs) are small proteins that are ubiquitously expressed in all organisms and implicated in several cellular ... ...

Abstract	Cold stress is a key environmental factor affecting plant growth and development, crop productivity, and geographic distribution. Thioredoxins (Trxs) are small proteins that are ubiquitously expressed in all organisms and implicated in several cellular processes, including redox reactions. However, their role in the regulation of cold stress in the halophyte plant
MeSH term(s)	Antioxidants/metabolism ; Brassicaceae/genetics ; Cell Membrane/metabolism ; Gene Expression Regulation, Plant ; Hydrogen Peroxide/metabolism ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Plants, Genetically Modified/genetics ; Plants, Genetically Modified/metabolism ; Reactive Oxygen Species/metabolism ; Salt-Tolerant Plants/genetics ; Stress, Physiological/genetics ; Nicotiana/metabolism ; Cold Temperature
Chemical Substances	Antioxidants ; Hydrogen Peroxide (BBX060AN9V) ; Plant Proteins ; Reactive Oxygen Species
Language	English
Publishing date	2023-02-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24033030
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Article ; Online: A Novel Therapeutic Approach to Treat Alzheimer's Disease by Neurotrophic Support During the Period of Synaptic Compensation.

Baazaoui, Narjes / Iqbal, Khalid

Journal of Alzheimer's disease : JAD

2018 Volume 62, Issue 3, Page(s) 1211–1218

Abstract: Alzheimer's disease (AD), at present, is considered an incurable disease and a major dilemma with no drug to stop or slow down its progression. Drugs that are currently available in the market are able to only transiently improve the clinical symptoms. ... ...

Abstract	Alzheimer's disease (AD), at present, is considered an incurable disease and a major dilemma with no drug to stop or slow down its progression. Drugs that are currently available in the market are able to only transiently improve the clinical symptoms. The repeated failures in developing an effective drug has led to the suggestion that the medical intervention was probably too late to be effective since the pathology starts many years before the appearance of the clinical symptoms. Probably, at the time of the appearance of clinical symptoms the brain has undergone major neuronal and synaptic loss. Because of the uncertainty on when to use a prevention therapy, especially targeting amyloid-β (Aβ) and tau pathologies, interventions that rely on the regenerative capacity of the brain such as the modulation of the inherent neurogenesis and neuronal plasticity represent a promising therapeutic strategy. Such an approach can act both at early as well as late stages of the disease and remove the barrier of the time of intervention. In this article, we review studies mainly from our laboratory that show the merit of early intervention during the synaptic and neuronal compensation period where the brain still has the capacity to self-repair by offering neurotrophic support in reversing cognitive impairment, neuronal and synaptic deficits, Aβ, and tau pathologies and decreasing mortality in a transgenic mouse model of AD.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/physiopathology ; Animals ; Brain/drug effects ; Brain/physiopathology ; Humans ; Nerve Growth Factors/pharmacology ; Nerve Growth Factors/therapeutic use ; Neuronal Plasticity/drug effects ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Synapses/drug effects ; Synapses/physiology
Chemical Substances	Nerve Growth Factors ; Neuroprotective Agents
Language	English
Publishing date	2018-03-20
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-170839
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Article: GASA Proteins: Review of Their Functions in Plant Environmental Stress Tolerance.

Bouteraa, Mohamed Taieb / Ben Romdhane, Walid / Baazaoui, Narjes / Alfaifi, Mohammad Y / Chouaibi, Yosra / Ben Akacha, Bouthaina / Ben Hsouna, Anis / Kačániová, Miroslava / Ćavar Zeljković, Sanja / Garzoli, Stefania / Ben Saad, Rania

Plants (Basel, Switzerland)

2023 Volume 12, Issue 10

Abstract: Gibberellic acid- ... ...

Abstract	Gibberellic acid-stimulated
Language	English
Publishing date	2023-05-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants12102045
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Article ; Online: Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound.

Baazaoui, Narjes / Iqbal, Khalid

Alzheimer's research & therapy

2017 Volume 9, Issue 1, Page(s) 45

Abstract: Background: The use of neurotrophic factors to treat Alzheimer's disease (AD) is hindered by their blood-brain barrier impermeability, short half-life, and severe side effects. Peptide 021 (P021) is a neurotrophic/neurogenic tetra-peptide that was ... ...

Abstract	Background: The use of neurotrophic factors to treat Alzheimer's disease (AD) is hindered by their blood-brain barrier impermeability, short half-life, and severe side effects. Peptide 021 (P021) is a neurotrophic/neurogenic tetra-peptide that was derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. Admantylated glycine was added to its C-terminal to increase its blood-brain barrier permeability and decrease its degradation by exopeptidases to make it druggable. Here, we report on the preventive effect of P021 in 3 × Tg-AD, a transgenic mouse model of AD. Methods: P021 was administered in the diet at 3 months, i.e., 6-9 months before any overt amyloid beta (Aβ) or tau pathology, and during the period of synaptic compensation, and was continued until 21 months in 3 × Tg-AD mice. The 3 × Tg-AD mice and wild-type (WT) mice were treated identically but with a vehicle-only diet serving as controls. The effects of P021 on neurogenesis, dendritic and synaptic markers, and cognitive performance were investigated. Results: We found that P021 treatment was able to rescue dendritic and synaptic deficits, boost neurogenesis, and reverse cognitive impairment in 3 × Tg-AD mice. Conclusions: Availability of appropriate neurotrophic support during the period of synaptic compensation can prevent synaptic deficit and cognitive impairment, and P021 is a promising neurotrophic compound for this purpose.
Language	English
Publishing date	2017-06-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-017-0273-7
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Article ; Online: Prevention of Amyloid-β and Tau Pathologies, Associated Neurodegeneration, and Cognitive Deficit by Early Treatment with a Neurotrophic Compound.

Baazaoui, Narjes / Iqbal, Khalid

Journal of Alzheimer's disease : JAD

2017 Volume 58, Issue 1, Page(s) 215–230

Abstract: To date, neither any effective treatment nor prevention of Alzheimer's disease (AD), a major dementia causing disorder, are available. Herein, we investigated the secondary prevention of neurodegeneration, amyloid-β (Aβ) and tau pathologies with a ... ...

Abstract	To date, neither any effective treatment nor prevention of Alzheimer's disease (AD), a major dementia causing disorder, are available. Herein, we investigated the secondary prevention of neurodegeneration, amyloid-β (Aβ) and tau pathologies with a neurotrophic compound P021 in 3xTg-AD mice. Previous work found that P021 can rescue at mild to moderate stages Aβ and tau pathologies in 3xTg-AD mice. To determine its potential clinical application, we sought to test the preventive effect of P021 on Aβ and tau pathologies by starting the treatment during the period of synaptic compensation several months before the appearance of any overt pathology in 3xTg-AD mice. We started a continuous treatment with P021 in 3-month-old female animals and followed its effect at 9-, 15- and 18-months post-treatment. Neurodegeneration at the above time points was studied using Fluorojade C staining, and tau and Aβ pathologies both immunohistochemically and by Western blots. Cognitive performance was studied by assessing episodic memory with Novel Object Recognition task at 16-17-months post-treatment. We found that P021 treatment initiated during the synaptic compensation period can prevent neurodegeneration, Aβ and tau pathologies, rescue episodic memory impairment, and markedly reduce mortality rate. These findings for the first time show effective prevention of AD changes with a neurotrophic compound that targets neurogenesis and synaptic plasticity, suggesting that improving the health of the neuronal network can prevent AD.
MeSH term(s)	Adamantane/analogs & derivatives ; Adamantane/chemistry ; Adamantane/therapeutic use ; Age Factors ; Alzheimer Disease/complications ; Alzheimer Disease/genetics ; Alzheimer Disease/prevention & control ; Amyloid beta-Protein Precursor/genetics ; Analysis of Variance ; Animals ; Cognition Disorders/etiology ; Cognition Disorders/prevention & control ; Disease Models, Animal ; Drug Administration Schedule ; Female ; Mice ; Mice, Transgenic ; Mutation/genetics ; Neurodegenerative Diseases/prevention & control ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/therapeutic use ; Oligopeptides/chemistry ; Oligopeptides/therapeutic use ; Presenilin-1/genetics ; Recognition (Psychology)/drug effects ; Tauopathies/genetics ; Tauopathies/prevention & control ; tau Proteins/genetics
Chemical Substances	Amyloid beta-Protein Precursor ; Neuroprotective Agents ; Oligopeptides ; P021 peptide ; Presenilin-1 ; tau Proteins ; Adamantane (PJY633525U)
Language	English
Publishing date	2017
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-170075
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Article ; Online: Vegetative Growth Dynamic and Its Impact on the Flowering Intensity of the Following Season Depend on Water Availability and Bearing Status of the Olive Tree

Sofiene B. M. Hammami / Manel Ben Laya / Narjes Baazaoui / Besma Sghaier-Hammami

Sustainability, Vol 14, Iss 15614, p

2022 Volume 15614

Abstract: A sufficient and mature vegetative growth is an essential condition for production in the following season and consequently affects the alternate bearing (AB) behavior. However, little is known about its interaction with the crop load and water supply. ... ...

Abstract	A sufficient and mature vegetative growth is an essential condition for production in the following season and consequently affects the alternate bearing (AB) behavior. However, little is known about its interaction with the crop load and water supply. Herein, we studied the effect of different water regimes and bearing status on the vegetative intensity and flush and its consequence on the flowering parameters of the following season. Rainfed (RF) and fully irrigated (FI) treatments were applied for bearing (ON) and non-bearing (OFF) trees of the ‘Zalmati’ olive orchard in south Tunisia during 2018. The water deficit condition (RF) and the high crop load (ON) have caused a similar decrease in the total node number and shoots length by about 65%. Furthermore, the flowering parameters in 2019, especially the percentage of floral buds (i.e., floral induction intensity), were differentially affected by water supply according to the bearing status of the previous season. FI reduced the percentage of floral buds in 2019 by about 37% for OFF trees, while it increased it by more than four times for the ON trees. Concerning the growth flush, the second (i.e., autumnal) flush seems to respond better to water supply than the first (i.e., spring) one, for both vegetative and flowering parameters. The second flush of growth provided 28% of the total vegetative growth but contributed about 35% to the total number of floral buds for RF OFF trees. Besides, FI makes the first and the second flushes contribute equally to total vegetative growth and to the flowering parameters of the following season. On the other hand, the bearing status of the trees does not affect the contribution of each flush to the total vegetative growth.
Keywords	Olea europaea ; water deficit ; alternate bearing ; year ON and OFF ; flower bud induction ; spring and autumnal growth flushes ; Environmental effects of industries and plants ; TD194-195 ; Renewable energy sources ; TJ807-830 ; Environmental sciences ; GE1-350
Subject code	580
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Functional Characterization of Lobularia maritima LmTrxh2 Gene Involved in Cold Tolerance in Tobacco through Alleviation of ROS Damage to the Plasma Membrane

Rania Ben Saad / Walid Ben Romdhane / Narjes Baazaoui / Mohamed Taieb Bouteraa / Yosra Chouaibi / Wissem Mnif / Anis Ben Hsouna / Miroslava Kačániová

International Journal of Molecular Sciences, Vol 24, Iss 3030, p

2023 Volume 3030

Abstract	Cold stress is a key environmental factor affecting plant growth and development, crop productivity, and geographic distribution. Thioredoxins (Trxs) are small proteins that are ubiquitously expressed in all organisms and implicated in several cellular processes, including redox reactions. However, their role in the regulation of cold stress in the halophyte plant Lobularia maritima remains unknown. We recently showed that overexpression of LmTrxh2 , which is the gene that encodes the h-type Trx protein previously isolated from L. maritima , led to an enhanced tolerance to salt and osmotic stress in transgenic tobacco. This study functionally characterized the LmTrxh2 gene via its overexpression in tobacco and explored its cold tolerance mechanisms. Results of the RT-qPCR and western blot analyses indicated differential temporal and spatial regulation of LmTrxh2 in L. maritima under cold stress at 4 °C. LmTrxh2 overexpression enhanced the cold tolerance of transgenic tobacco, as evidenced by increased germination rate, fresh weight and catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) activities; reduced malondialdehyde levels, membrane leakage, superoxide anion (O 2 − ), and hydrogen peroxide (H 2 O 2 ) levels; and higher retention of chlorophyll than in non-transgenic plants (NT). Furthermore, the transcript levels of reactive oxygen species (ROS)-related genes ( NtSOD and NtCAT1 ), stress-responsive late embryogenis abundant protein 5 ( NtLEA5 ), early response to dehydration 10C ( NtERD10C ), DRE-binding proteins 1A ( NtDREB1A ), and cold-responsive ( COR ) genes ( NtCOR15A , NtCOR47 , and NtKIN1 ) were upregulated in transgenic lines compared with those in NT plants under cold stress, indicating that LmTrxh2 conferred cold stress tolerance by enhancing the ROS scavenging ability of plants, thus enabling them to maintain membrane integrity. These results suggest that LmTrxh2 promotes cold tolerance in tobacco and provide new insight into the improvement of cold-stress resistance to cold stress ...
Keywords	LmTrxh2 ; cold stress ; membrane integrity ; Lobularia maritima ; reactive oxygen species ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	580
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.

Alkafaas, Samar Sami / Elsalahaty, Mohamed I / Ismail, Doha F / Radwan, Mustafa Ali / Elkafas, Sara Samy / Loutfy, Samah A / Elshazli, Rami M / Baazaoui, Narjes / Ahmed, Ahmed Ezzat / Hafez, Wael / Diab, Mohanad / Sakran, Mohamed / El-Saadony, Mohamed T / El-Tarabily, Khaled A / Kamal, Hani K / Hessien, Mohamed

Cancer cell international

2024 Volume 24, Issue 1, Page(s) 89

Abstract: Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells ... ...

Abstract	Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein-protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis.
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2091573-1
ISSN	1475-2867
ISSN	1475-2867
DOI	10.1186/s12935-024-03221-8
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