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BIN1 in the Pursuit of Ousting the Alzheimer’s Reign: Impact on Amyloid and Tau Neuropathology

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Abstract

Alzheimer’s disease contributes to 60–70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer’s disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.

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Abbreviations

BIN1:

Bridging integrator 1

APOE:

Apolipoprotein E

AD:

Alzheimer disease

Aβ:

Amyloid beta

BACE1:

Beta-secretase 1

APP:

Amyloid precursor protein

GWAS:

Genome-wide association studies

CLAP:

Clathrin and AP2 binding

EEA1:

Early endosome antigen 1

CTF:

C-terminal fragments

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Authors and Affiliations

  1. College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

    Ishnoor Kaur

  2. School of Health Sciences and Technology, University of Petroleum and Energy Studies, Bidholi, Dehradun, India

    Tapan Behl

  3. Department of Pharmaceutics, Faculty of Pharmacy, Sree Balaji Medical College and Hospital, Chromepet, Chennai, Tamil Nadu, India

    G. Sundararajan

  4. Faculty of Pharmacy, Sree Balaji Medical College and Hospital Campus, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India

    P. Panneerselvam, A. R. Vijayakumar & G. P. Senthilkumar

  5. Department of Pharmaceutical Chemistry, JKKMMRFs-Amnai JKK Sampoorani Ammal College of Pharmacy, Komarapalayam, Tamil Nadu, India

    T. Venkatachalam

  6. Faculty of Pharmaceutical Sciences, DAV University, Jalandhar, Punjab, India

    Dharmender Jaglan

  7. School of Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Chhatrapti Shahu Ji Maharaj University, Uttar Pradesh, Kanpur, India

    Shivam Yadav

  8. Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia

    Khalid Anwer

  9. Faculty of Pharmacy, AIMST University, Bedong, Kedah, Malaysia

    Neeraj Kumar Fuloria

  10. Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospital, Saveetha University, Chennai, Tamil Nadu, India

    Neeraj Kumar Fuloria

  11. GHG Khalsa College of Pharmacy, Gurusar Sadhar, Punjab, India

    Aayush Sehgal

  12. School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 1444411, India

    Monica Gulati

  13. Faculty of Health, ARCCIM, University of Technology Sydney, Ultimo, NSW, 20227, Australia

    Monica Gulati

  14. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah, 52571, Kingdom of Saudi Arabia

    Sridevi Chigurupati

  15. Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Saveetha Nagar, Thandalam, Chennai, Tamilnadu, 602105, India

    Sridevi Chigurupati

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  1. Ishnoor Kaur
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  2. Tapan Behl
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Contributions

IK and TB: conceived the study and wrote the article; GS, PP, ARV, and GPS: literature review; SY and MKA: editing; AS: figure work; MG: revision; TB, NKF, and SC: proof read.

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Correspondence to Tapan Behl or Sridevi Chigurupati.

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Highlights

• BIN1 in Aβ accumulation: variants impact on early endosome size, Aβ profile, BACE1 and endocytic signaling.

• BIN1 in tau accumulation: impact on spine morphology and release of tau.

• BIN1 and synaptic transmission liaisons.

• Future prospects of BIN1 in AD.

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Kaur, I., Behl, T., Sundararajan, G. et al. BIN1 in the Pursuit of Ousting the Alzheimer’s Reign: Impact on Amyloid and Tau Neuropathology. Neurotox Res 41, 698–707 (2023). https://doi.org/10.1007/s12640-023-00670-3

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