The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease

Iqbal, Umar; Zeng, Emma; Pasinetti, Giulio Maria

doi:10.3390/ijms21144920

Cited by 35 publications

(30 citation statements)

References 152 publications

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“…These prodromal stages are the best time/targets for prevention or disease-modifying treatments; however, the lack of real biomarkers needs to be addressed before the development of any treatment. 5 …”

Section: What Is Alzheimer’s Disease?mentioning

confidence: 99%

“…As we are specifically interested here in the antimicrobial defense in the brain, we will consider the fight against infections and inflammation in a chronic setting. 5 We will describe what treatment options exist and what is in the pipeline considering these pathological processes.…”

Section: What About Interventions?mentioning

confidence: 99%

“…These prodromal stages are the best time/targets for prevention or diseasemodifying treatments; however, the lack of real biomarkers needs to be addressed before the development of any treatment. 5 Pathologically AD is a neurodegenerative disease with a very long development history that can last decades. 6 AD is likely a syndrome as it seems that many different causes can lead to its development.…”

Section: What Is Alzheimer's Disease? Clinicallymentioning

confidence: 99%

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Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

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Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.

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Section: What Is Alzheimer’s Disease?mentioning

confidence: 99%

Section: What About Interventions?mentioning

confidence: 99%

Section: What Is Alzheimer's Disease? Clinicallymentioning

confidence: 99%

See 1 more Smart Citation

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

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“…Amyloid-forming peptides are the classic example of peptides that undergo a conformational transition from the native, mainly α-helical structure into an isoform with high beta-sheet content. They share key structural and functional features with AMPs [ 31 ]. Although some amyloid-forming peptides possess antimicrobial potency [ 32 ], they are well studied, mainly because they are considered to be immediate precursors for the formation of amyloid fibers and so are the most toxic components in many neurodegenerative diseases.…”

Section: Secondary Structure and Self-aggregationmentioning

confidence: 99%

Physicochemical Features and Peculiarities of Interaction of AMP with the Membrane

Pirtskhalava¹,

Vishnepolsky²,

Grigolava³

et al. 2021

Pharmaceuticals

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Antimicrobial peptides (AMPs) are anti-infectives that have the potential to be used as a novel and untapped class of biotherapeutics. Modes of action of antimicrobial peptides include interaction with the cell envelope (cell wall, outer- and inner-membrane). A comprehensive understanding of the peculiarities of interaction of antimicrobial peptides with the cell envelope is necessary to perform a rational design of new biotherapeutics, against which working out resistance is hard for microbes. In order to enable de novo design with low cost and high throughput, in silico predictive models have to be invoked. To develop an efficient predictive model, a comprehensive understanding of the sequence-to-function relationship is required. This knowledge will allow us to encode amino acid sequences expressively and to adequately choose the accurate AMP classifier. A shared protective layer of microbial cells is the inner, plasmatic membrane. The interaction of AMP with a biological membrane (native and/or artificial) has been comprehensively studied. We provide a review of mechanisms and results of interactions of AMP with the cell membrane, relying on the survey of physicochemical, aggregative, and structural features of AMPs. The potency and mechanism of AMP action are presented in terms of amino acid compositions and distributions of the polar and apolar residues along the chain, that is, in terms of the physicochemical features of peptides such as hydrophobicity, hydrophilicity, and amphiphilicity. The survey of current data highlights topics that should be taken into account to come up with a comprehensive explanation of the mechanisms of action of AMP and to uncover the physicochemical faces of peptides, essential to perform their function. Many different approaches have been used to classify AMPs, including machine learning. The survey of knowledge on sequences, structures, and modes of actions of AMP allows concluding that only possessing comprehensive information on physicochemical features of AMPs enables us to develop accurate classifiers and create effective methods of prediction. Consequently, this knowledge is necessary for the development of design tools for peptide-based antibiotics.

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“…In addition, most AD patients are diagnosed in the middle-to-late-stages of this disorder when irreversible damage to the brain has already occurred, and the "pre-clinical" or "prodromal" phase has already passed. More recently therapeutic approaches and disease modification strategies directed against other AD-implicated pathological mechanisms, including alterations in tau signaling, the cholinergic system, anti-microbial and anti-viral approaches and hormone replacement therapies, to name a few, may provide improved clinical efficacy (Bhute et al, 2020;Habes et al, 2020;Hampel et al, 2020a,b;Iqbal et al, 2020;Zhou et al, 2020).…”

Section: Mirna For Precision Medicine-based Diagnostics and Therapeuticsmentioning

confidence: 99%

microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

et al. 2020

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Alzheimer's disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression patterns in brain tissues, the systemic circulation, the extracellular fluid (ECF) and the cerebrospinal fluid (CSF). miRNAs have been investigated as candidate biomarkers for AD diagnosis, disease prediction, prognosis and therapeutic purposes because of their involvement in multiple brain signaling pathways in both health and disease. In this review we will: (i) highlight the significantly heterogeneous nature of miRNA expression and complexity in AD tissues and biofluids; (ii) address how information may be extracted from these data to be used as a diagnostic, prognostic and/or screening tools across the entire continuum of AD, from the preclinical stage, through the prodromal, i.e., mild cognitive impairment (MCI) phase all the way to clinically overt dementia; and (iii) consider how specific miRNA expression patterns could be categorized using miRNA reporters that span AD pathophysiological initiation and disease progression.

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The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease

Cited by 35 publications

References 152 publications

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Physicochemical Features and Peculiarities of Interaction of AMP with the Membrane

microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

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