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Exploring the molecular role of endostatin in diabetic neuropathy

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Abstract

For over a decade, diabetic neuropathy has exhibited great emergence in diabetic patients. Though there are numerous impediments in understanding the underlying pathology it is not that enough to conclude. Initially, there was no intricate protocol for diagnosis as its symptoms mimic most of the neurodegenerative disorders and demyelinating diseases. Continuous research on this, reveals many pathological correlates which are also detectable clinically. The most important pathologic manifestation is imbalanced angiogenesis/neo-vascularization. This review is completely focused on established pathogenesis and anti-angiogenic agents which are physiological signal molecules by the origin. Those agents can also be used externally to inhibit those pathogenic pathways. Pathologically DN demonstrates the misbalanced expression of many knotty factors like VEGF, FGF2, TGFb, NF-kb, TNF-a, MMP, TIMP, and many minor factors. Their pathway towards the incidence of DN is quite interrelated. Many anti-angiogenic agents inhibit neovascularization to many extents, but out of them predominantly inhibition of angiogenic activity is shared by endostatin which is now in clinical trial phase II. It inhibits almost all angiogenic factors and it is possible because they share interrelated pathogenesis towards imbalanced angiogenesis. Endostatin is a physiological signal molecule produced by the proteolytic cleavage of collagen XVIII. It has also a broad research profile in the field of medical research and further investigation can show promising therapeutic effects for benefit of mankind.

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Abbreviations

AGE:

Advanced glycation end products

DM:

Diabetic mellitus

DN:

Diabetic neuropathy

DPN:

Diabetic peripheral neuropathy

DSPN:

Diabetic sensory poly neuropathy

ELK-1:

ETS transcription factor

eNOs:

Endothelial NO synthase

ERK:

Extracellular receptor kinase

FAK:

Focal adhesion kinase

FGF2:

Fibroblast growth factor

GRB:

Growth factor receptor bound protein

ICAM:

Inter-cellular adhesion molecule

IGF:

Insulin-like growth factor

IRS:

Insulin receptor substrate

MAPK:

Mitogen activated protein kinase

MER:

Proto oncogene

MMP:

Matrix metallopeptidases

NCV:

Nerve conduction velocity

NF-kb:

Nuclear factor kappa beta

NGF:

Nerve growth factor

PARP:

Poly (ADP-ribose) polymerase

PDGFR:

Platelet-derived growth factor receptor

PIGF:

Placental growth factor

RAF-1:

Rapidly accelerated fibrosarcoma

RAGE:

Receptor for advanced glycation end products

RAS:

Term comes from Rat Sarcoma

ROS:

Reactive oxygen species

SOS:

Son of sevenless

Src:

Oncoprtotein named by the short form of ‘sarcoma’

SRF:

Serum response factor

TGFb:

Transforming growth factor beta

TIMP:

Tissue inhibitor of metalloproteinase

TNF-a:

Tumor necrosis factor alpha

uPA-uPAR:

Urokinase type plasminogen activator and receptor

VEGF:

Vascular endothelial growth factor

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  1. Tuhin Mukherjee and Tapan Behl have contributed equally.

Authors and Affiliations

  1. Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, India

    Tuhin Mukherjee

  2. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Tapan Behl, Aayush Sehgal & Harmanpreet Singh

  3. Amity Institute of Pharmacy, Amity University, Gurgaon, Haryana, India

    Saurabh Bhatia

  4. Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman

    Saurabh Bhatia

  5. Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania

    Simona Bungau

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  1. Tuhin Mukherjee
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  4. Saurabh Bhatia
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TM and TB: Conceived the idea and wrote the first draft; AS and SB: Review of literature and figure work; HS: Data compilation; SB: Proof Read.

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Correspondence to Tapan Behl.

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Mukherjee, T., Behl, T., Sehgal, A. et al. Exploring the molecular role of endostatin in diabetic neuropathy. Mol Biol Rep 48, 1819–1836 (2021). https://doi.org/10.1007/s11033-021-06205-3

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