FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: peripheral neuropathy, drug-induced
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General Information
Name
peripheral neuropathy, drug-induced
FlyBase ID
FBhh0000755
Disease Ontology Term
Parent Disease
OMIM
Overview

Drug-induced peripheral neuropathy is a common condition caused by many different prescribed medications. Drosophila models have been used to investigate chemotherapy-induced peripheral neuropathy (CIPN), characterizing the neurotoxicity of the chemotherapeutic drugs taxol, cisplatin, and bortezomib, and peripheral neuropathy induced by antiretroviral therapy (ART).

Effects of taxol (paclitaxel) have been assessed in larvae fed the drug. Axonal injury following taxol treatment is apparent within 3 days, with maximal injury after 4 days; the observed neurodegeneration was determined to be independent of apoptosis. In a screen to isolate loss-of-function mutations that block taxol-induced axonal degeneration, the Dmel\rtp gene was identified; the orthologous MORN4 gene was investigated in mammalian systems. In investigating paclitaxel, it was found that overexpression of the Dmel\Nmnat gene (orthologous to human NMNAT genes) or loss of Dmel\wnd (wallenda, orthologous to human MAP3K12/13) ameliorates deleterious effects.

To study cisplatin-induced neurotoxicity, adult flies were exposed to different levels of cisplatin for 3 days and observed for survival and geotactic climbing behavior, cisplatin-DNA binding, and cellular apoptosis. At a moderate dose, significant reduction in climbing ability was observed by day 3 with little lethality; the highest dose resulted in 100% lethality. In contrast to findings with taxol, dose-dependent induction of neuronal apoptosis was observed. Targeted expression of the anti-apoptotic baculoviral protein p35 (BacA\p35) prevented cisplatin-induced apoptosis in the brain and restored climbing behavior.

Effects of bortezomib have been assessed in larvae fed the drug. Assessed in larval nociceptive neurons, bortezomib was found to inhibit dynamic microtubule behavior.

Nucleoside reverse transcriptase inhibitor antiretrovirals AZT (Zidovudine or Azidothymidine) and ddC (Zalcitabine) were initially characterized using a behavioral response of larvae when exposed to noxious stimuli. Impact upon morphology and response of peripheral sensory neurons were assessed and compared to that observed for taxol; key differences were detected. Pathways known to suppress peripheral neuropathy induced by chemotherapeutic drugs were found to be ineffective in suppressing the peripheral neuropathy induced by these antiretrovirals.

See the FlyBase chemical reports for cisplatin (FBch0000748), bortezomib (FBch0000415), paclitaxel (taxol, FBch0000460), doxorubicin (FBch0000426), cyclophosphamide, (FBch0000076), zalcitabine (FBch0000998), zidovudine (FBch0000997), niclosamide (FBch0001307).

[updated Mar. 2024 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: peripheral neuropathy, drug-induced
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Peripheral neuropathies are characterized by degeneration of peripheral motor, sensory and/or autonomic axons, leading to progressive distal muscle weakness, sensory deficits and/or autonomic dysfunction. Acquired peripheral neuropathies, e.g., as a side effect of chemotherapy, are distinguished from inherited peripheral neuropathies (FBrf0235625 and references cited therein).

(FlyBase Curators, 2013-)

Drug-induced peripheral neuropathy (DIPN) is a common and painful condition caused by many different and frequently prescribed medications. Most often, DIPN is seen in chemotherapeutic agents, antimicrobials, cardiovascular drugs, psychotropic, and anticonvulsant drugs (Jones, et al., 2020; pubmed:30666914).

(FlyBase Curators, 2013-)

Symptoms of peripheral sensory neuropathy (PSN) include pain and/or numbness in the extremities.

(FlyBase Curators, 2013-)
Genetics
Cellular phenotype and pathology
Molecular information
External links
    Disease synonyms
    acquired peripheral neuropathy
    CIPN
    DIPN
    drug-induced peripheral neuropathy
    peripheral neuropathy, chemotherapy-induced
    peripheral neuropathy, drug-induced
    peripheral sensory neuropathy, antiretroviral-induced
    PSN, drug-induced
    toxic neuropathy
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (0)
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (0 groups)
          Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
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          Bloomington Stock Center Disease Page
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          Publicly Available Stocks
          Selected Drosophila transgenes
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          References (24)