Lapatinib ditosylate rescues motor deficits in rotenone-intoxicated rats: Potential repurposing of anti-cancer drug as a disease-modifying agent in Parkinson's disease

Mansour, Heba M.; Mohamed, Abdullah; Khattab, Mahmoud M.; El-Khatib, Aiman S.

doi:10.1016/j.ejphar.2023.175875

Cited by 13 publications

(2 citation statements)

References 92 publications

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“…Activates GPX4/GSH/NRF2 axis; inhibits oxidative markers, including iron, TfR1, PTGS2, and 4-HNE; and suppresses p-EGFR/c-SRC/PKCβII/PLC-γ/ACSL-4 pathway [119].…”

Section: Lapatinibmentioning

confidence: 99%

The Role of Calcium and Iron Homeostasis in Parkinson’s Disease

Wang,

Zhao,

Zhao

et al. 2024

Brain Sciences

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Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there are currently no viable treatment options or effective strategies to cure and delay progression. Pathological hallmarks of PD, such as dopaminergic neuronal death and intracellular α-synuclein deposition, are closely involved in perturbations of iron and calcium homeostasis and accumulation. Here, we summarize the mechanisms by which Ca2+ signaling influences or promotes PD progression and the main mechanisms involved in ferroptosis in Parkinson’s disease. Understanding the mechanisms by which calcium and iron imbalances contribute to the progression of this disease is critical to developing effective treatments to combat this devastating neurological disorder.

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“…Activates GPX4/GSH/NRF2 axis; inhibits oxidative markers, including iron, TfR1, PTGS2, and 4-HNE; and suppresses p-EGFR/c-SRC/PKCβII/PLC-γ/ACSL-4 pathway [119].…”

Section: Lapatinibmentioning

confidence: 99%

The Role of Calcium and Iron Homeostasis in Parkinson’s Disease

Wang,

Zhao,

Zhao

et al. 2024

Brain Sciences

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“…Furthermore, lapatinib had an impact on proteins such as LRKK2, α-syn, and c-ABL, resulting in the restoration of dopamine levels as well as the suppression of ferroptosis and lipid peroxidation. This study highlights the potential of targeting the HSP90/CDC37 complex to activate the antioxidant system [177], although it is crucial to consider its possible impact on glutathione (GSH) levels, which also play a role in PD pathogenesis [178].…”

Section: Pharmacological Modulation Of Hsps and Neuroprotective Effec...mentioning

confidence: 99%

Modulating Stress Proteins in Response to Therapeutic Interventions for Parkinson’s Disease

Silvestro,

Raffaele,

Mazzon

2023

IJMS

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Parkinson’s disease (PD) is a neurodegenerative illness characterized by the degeneration of dopaminergic neurons in the substantia nigra, resulting in motor symptoms and without debilitating motors. A hallmark of this condition is the accumulation of misfolded proteins, a phenomenon that drives disease progression. In this regard, heat shock proteins (HSPs) play a central role in the cellular response to stress, shielding cells from damage induced by protein aggregates and oxidative stress. As a result, researchers have become increasingly interested in modulating these proteins through pharmacological and non-pharmacological therapeutic interventions. This review aims to provide an overview of the preclinical experiments performed over the last decade in this research field. Specifically, it focuses on preclinical studies that center on the modulation of stress proteins for the treatment potential of PD. The findings display promise in targeting HSPs to ameliorate PD outcomes. Despite the complexity of HSPs and their co-chaperones, proteins such as HSP70, HSP27, HSP90, and glucose-regulated protein-78 (GRP78) may be efficacious in slowing or preventing disease progression. Nevertheless, clinical validation is essential to confirm the safety and effectiveness of these preclinical approaches.

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