Focus on the Multimodal Role of Autophagy in Rheumatoid Arthritis
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REVIEW
Focus on the Multimodal Role of Autophagy in Rheumatoid Arthritis Swati Chadha,1 Tapan Behl ,1,4 Simona Bungau,2,4 Arun Kumar,1 Rajwinder Kaur,1 Thangaval Venkatachalam,3 Amit Gupta,1 Mimansa Kandhwal,1 and Deepak Chandel1 Received 11 July 2020; accepted 17 August 2020
Abstract— Autophagy exerts its dual role in eukaryotic cells and exerts its cytoprotective a-
ction through degradation mechanism and by regulating catabolic processes which results in elimination of pathogens. Under suitable conditions, autophagy is associated with recycling of cytoplasmic components which causes regeneration of energy whereas deregulated autophagy exerts its implicated role in development and pathogenesis of auto-immune diseases such as rheumatoid arthritis. The immune, innate, and adaptive responses are regulated through the development, proliferation, and growth of lymphocytes. Such innate and adaptive responses can act as mediator of arthritis; along with this, stimulation of osteoclast-mediated bone resorption takes place via transferring citrullinated peptides towards MHC (major histocompatibility complex) compartments, thereby resulting in degradation of bone. Processes such as apoptosis resistance are also regulated through autophagy. In this review, the current knowledge based on role of autophagy in pathogenesis of rheumatoid arthritis is summarized along with proteins associated. KEY WORDS: auto-immune; autophagy; rheumatoid arthritis; immune response.
INTRODUCTION Autophagy can be defined as a degradation pathway which can be characterized via isolating the specific cytoplasmic material in a double membrane vesicle termed as
Swati Chadha, Tapan Behl, Simona Bungau and Rajwinder Kaur contributed equally to this work. 1
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India 2 Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania 3 JKKMMRF College of Pharmacy, Tiruchengode, Tamil Nadu, India 4 To whom correspondence should be addressed to Tapan Behl at Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India. E-mail: [email protected]; and ; [email protected]
autophagic vacuole (autophagosome), followed via the fusion of autophagic vesicle with that of lysosome which ensures destruction of organelles as well as misfolded proteins, further carried inside vesicles [1]. Autophagy can be defined as a physiological process which is required for the degradation of proteins and is restricted towards tissue. It can be considered as a physiological process which is involved in turning over of basal organelles and is required for removing the protein aggregates [2]. The process of autophagy is considered as cellular housekeeping pathway, pro-survival mechanism which exerts its major action of removing or eliminating damaged organelles and aggregates of proteins [3, 4]. Along with the removal of aggregated proteins, it serves and provides energy that is employed for synthesizing macromolecules as in case of starvation and during excessive
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