Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease

Khan, Sahil; Barve, Kalyani; Kumar, Maushmi S.

doi:10.2174/1570159x18666200528142429

Cited by 410 publications

(330 citation statements)

References 127 publications

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“…It is a progressive disorder that causes severe cognitive dysfunctions and decline of memory. The molecular basis of AD is related with β-amyloid (Aβ) plaques accumulation in the brain and hyperphosphorylated tau-containing neurofibrillary tangles within the neurons [ 100 ].…”

Section: Neurojanus Role Of P62mentioning

confidence: 99%

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

Emanuele

Lauricella

D’Anneo

et al. 2020

IJMS

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p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targeting the selected cargo to the autophagosome with consequent autophagic degradation. Beside this function, p62 behaves as an interactive hub in multiple signalling including those mediated by Nrf2, NF-κB, caspase-8, and mTORC1. The protein is thus crucial for the control of oxidative stress, inflammation and cell survival, apoptosis, and metabolic reprogramming, respectively. As a multifunctional protein, p62 falls into the category of those factors that can exert opposite roles in the cells. Chronic p62 accumulation was found in many types of tumors as well as in stress granules present in different forms of neurodegenerative diseases. However, the protein seems to have a Janus behaviour since it may also serve protective functions against tumorigenesis or neurodegeneration. This review describes the diversified roles of p62 through its multiple domains and interactors and specifically focuses on its oncoJanus and neuroJanus roles.

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Section: Neurojanus Role Of P62mentioning

confidence: 99%

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

Emanuele

Lauricella

D’Anneo

et al. 2020

IJMS

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“…Many factors have been associated with AD, such as inflammation, oxidative stress, metabolic disturbances and the imbalance of neurotransmitters [ 26 , 27 ]. Inflammatory reactions and oxidation are consequences of the activation of microglia and/or astrocytes that are induced by changes associated with the accumulation of aberrant proteins.…”

Section: Alzheimer’s Disease Etiopathologymentioning

confidence: 99%

Natural Bioactive Products and Alzheimer’s Disease Pathology: Lessons from Caenorhabditis elegans Transgenic Models

Navarro-Hortal¹,

Romero-Márquez²,

Osta³

et al. 2022

Diseases

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Alzheimer’s disease (AD) is an age-dependent, progressive disorder affecting millions of people. Currently, the therapeutics for AD only treat the symptoms. Although they have been used to discover new products of interest for this disease, mammalian models used to investigate the molecular determinants of this disease are often prohibitively expensive, time-consuming and very complex. On the other hand, cell cultures lack the organism complexity involved in AD. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of human AD. Numerous models of both Tau- and Aβ-induced toxicity, the two prime components observed to correlate with AD pathology and the ease of performing RNA interference for any gene in the C. elegans genome, allow for the identification of multiple therapeutic targets. The effects of many natural products in main AD hallmarks using these models suggest promising health-promoting effects. However, the way in which they exert such effects is not entirely clear. One of the reasons is that various possible therapeutic targets have not been evaluated in many studies. The present review aims to explore shared therapeutical targets and the potential of each of them for AD treatment or prevention.

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“…In recent years, AI/ML‐based models have become popular in AD research, mostly utilizing for AD diagnosis and prognosis in dealing with electronic health records and images 412 . On the contrary, AI/ML techniques have not been widely employed in AD drug discovery.…”

Section: Ai/ml Applications In Cns Drug Discoverymentioning

confidence: 99%

Artificial intelligence and machine learning‐aided drug discovery in central nervous system diseases: State‐of‐the‐arts and future directions

Vatansever

Schlessinger

Wacker

et al. 2020

Medicinal Research Reviews

217

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Neurological disorders significantly outnumber diseases in other therapeutic areas. However, developing drugs for central nervous system (CNS) disorders remains the most challenging area in drug discovery, accompanied with the long timelines and high attrition rates. With the rapid growth of biomedical data enabled by advanced experimental technologies, artificial intelligence (AI) and machine learning (ML) have emerged as an indispensable tool to draw meaningful insights and improve decision making in drug discovery. Thanks to the advancements in AI and ML algorithms, now the AI/ML‐driven solutions have an unprecedented potential to accelerate the process of CNS drug discovery with better success rate. In this review, we comprehensively summarize AI/ML‐powered pharmaceutical discovery efforts and their implementations in the CNS area. After introducing the AI/ML models as well as the conceptualization and data preparation, we outline the applications of AI/ML technologies to several key procedures in drug discovery, including target identification, compound screening, hit/lead generation and optimization, drug response and synergy prediction, de novo drug design, and drug repurposing. We review the current state‐of‐the‐art of AI/ML‐guided CNS drug discovery, focusing on blood–brain barrier permeability prediction and implementation into therapeutic discovery for neurological diseases. Finally, we discuss the major challenges and limitations of current approaches and possible future directions that may provide resolutions to these difficulties.

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Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease

Cited by 410 publications

References 127 publications

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

Natural Bioactive Products and Alzheimer’s Disease Pathology: Lessons from Caenorhabditis elegans Transgenic Models

Artificial intelligence and machine learning‐aided drug discovery in central nervous system diseases: State‐of‐the‐arts and future directions

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