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Advanced Neurology Graphene quantum dots approach in AD

The top-down approach begins with large-scale carbon films that constitute the components of GQDs. Figure 1
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materials such as multi-walled carbon nanotubes, summarizes these top-down and bottom-up approaches
graphene oxide (GO), or graphite. These bulk materials for the synthesis of GQDs. A study by Wang et al. found
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are then broken down into smaller GQDs using techniques that GQDs play a vital role in preventing the accumulation
such as chemical reactions, heat treatment, or physical of islet amyloid polypeptide (IAPP) in embryonic zebrafish,
methods. This approach generally allows for high yield suggesting their potential to inhibit amyloid aggregation.
and scalability. Specific steps in this process include pulsed In the presence of GQDs, IAPP helices were absorbed onto
laser ablation, electrochemical cutting, and reduction or the surface of GQD sheets and temporarily unfolded after a
oxidation cutting reactions. Oxidative cutting is one of sequence of thermodynamic perturbations. This disrupted
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the most commonly used methods for the synthesis of the helical and sheet structures of IAPP, producing
GQDs. It involves the chemical oxidation of graphene, GO, disordered and random monomers, thereby preventing
or carbon nanotubes using strong oxidizing agents such as amyloid-related disorders. 37
sulfuric acid, nitric acid, or potassium permanganate. The
oxidants disrupt the sp structure of graphene into smaller, 4. Pathogenesis of AD
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oxygen-rich fragments, which are subsequently reduced 4.1. Amyloid cascade
to restore conductivity. Another top-down approach for Aβ peptide has been recognized as a fundamental initiator of
the synthesis of GQDs is hydrothermal cutting, in which AD, with its accumulation and aggregation driven by either
GO is hydrothermally treated in an autoclave at high excessive production or impaired removal mechanisms. Aβ
temperatures (120 – 200°C), leading to the fragmentation originates from the amyloid pre-cursor protein (APP) via
of GO into GQDs. Hydrothermal techniques utilize sequential cleavage by β-secretase and γ-secretase enzymes.
solvents, such as ethanol or ethylene glycol to modify the Its clearance relies mainly on lysosomal degradation and
surface properties of GQD. Both approaches are simple proteolytic systems. Structurally, Aβ is a transmembrane
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and scalable methods for the mass production of GQDs. peptide composed of approximately 39 – 43 amino acids
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Graphite electrodes can also undergo electrochemical and exists in various biochemical forms. Aβ is produced
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oxidation in alkaline solutions such as sodium hydroxide, through the proteolysis of the APP, which is first cleaved
potassium hydroxide, or sulfuric acid under an applied by β-secretase and then by γ-secretase through the
voltage. This top-down approach leads to the exfoliation amyloidogenic pathway. APP can undergo processing via
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and production of highly fluorescent GQDs. 39,40 Ultrasonic three distinct pathways. The first is the non-amyloidogenic
exfoliation is another top-down approach that involves the pathway, which involves α- and γ-secretases and generates
breakdown of graphene sheets into smaller GQD fragments neuroprotective fragments such as soluble APPα and
using ultrasonic waves in either acidic or aqueous C-terminal fragment α. In contrast, the amyloidogenic
solutions. This method is cost-effective and eliminates pathway employs β-secretase and γ-secretase, producing
the use of harsh chemicals. The bottom-up method for neurotoxic fragments, particularly various lengths of
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synthesizing GQDs involves the molecular grouping Aβ peptides. The third route involves η-secretase under
of carbon pre-cursors to form GQDs, allowing precise physiological conditions. Aβ peptides mainly exist as
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control over size, composition, and functional groups. two primary isoforms: the soluble Aβ40 and the insoluble,
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A major technique in this approach is the carbonization more aggregation-prone, and neurotoxic Aβ42. In normal
of molecular pre-cursors, in which organic molecules physiological conditions, Aβ40 comprises more than 90%
such as citric acid, glucose, and polyethylene glycol are of total Aβ, whereas Aβ42 remains under 5%. Excessive
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heated at high temperatures (200 – 400°C). This process aggregation of Aβ42 significantly contributes to neuronal
induces the dehydration and carbonization of organic toxicity, triggering reactive oxidative species production.
molecules (known as pyrolysis), forming GQDs. Pyrolysis These free radicals can oxidize proteins and lipids, altering
involves heating organic materials such as polycyclic their functions and producing harmful oxidized proteins
aromatic hydrocarbons or glucose in an inert atmosphere and lipid peroxides. Such oxidative alterations can disrupt
to form crystalline GQDs. Microwave-assisted synthesis neuronal enzymes, such as glutamine synthetase and
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is another bottom-up approach that involves the use creatine kinase, which are crucial for normal neuron
of microwave irradiation to rapidly carbonize organic function. 49,50 Lipid peroxidation further generates toxic
pre-cursors, leading to the rapid formation of GQDs. metabolites such as 4-hydroxy-2-nonenal and acrolein,
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Another technique in this approach is chemical vapor leading to disrupted calcium balance, impaired ion-motive
deposition, where hydrocarbon gases, such as methylene or ATPases, reduced glutamate uptake by glial cells, and
methane are decomposed at high temperatures over metal interrupted neuronal signaling pathways, cumulatively
catalysts, such as copper and nickel, forming graphene resulting in neuronal cell death. Histopathologically,
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Volume 4 Issue 4 (2025) 20 doi: 10.36922/an.7087